ENDOCRINOLOGY
HYPOPITUITARISM
Etiology
Q
Sheehan syndrome
• Post partum pituitary
necrosis
• Cause: Severe post partum
haemorrhage
• History of multiple blood
transfusion during delivery /
labour
• Mother presents with
lactation failure
• Deficiency of GH,
prolactin, TSH (central
hypothyroidism)
• Investigation: MRI → empty
sella is seen
• Normally ACTH /
gonadotropin spared in
Sheehan syndrome, but
incase if rarely ACTH
deficiency is seen, we replace
cortisol with hydrocortisone
• Gold standard -
insulin tolerance test
(contraindications: coronary
artery disease, seizure)
• Other tests - glucagon
stimulation test, GHRH
arginine test, macimorelin
stimulation test
– Serum prolactin
Estimation test to
detect prolactin
deficiency & simple
thyroid function testing
to check central
hypothyroidism (T3, 4
low, normal or decrease
TSH)
Apoplexy RT Infiltration
• Haemorrhage in the • More sensitive: • 3 main examples:
Q
pituitary Hypothalamus > – Sarcoidosis,
• Cause: 90% due to pituitary – Hemochromatosis,
pituitary macro adenoma • If radiation is >12-18 – Langerhans cell
• Other causes: DIC, gy: GH affected first, histiocytosis
Malignant hypotension, mainly somatotropes • Mainly damage anterior
trauma, coagulopathy • If radiation is >30 pituitary
• Clinical features: gy: lead to multiple • Patients presents with
nausea, vomiting, intense pituitary hormone central DI, polyuria,
headache because of deficiency polydypsia
raised ICP, diplopia • History of childhood • Sarcoidosis can lead to
due to 6th CN damage, brain tumor central & Nephrogenic
visual field defect, DI
Q
Adrenal insufficiency • Lymphocytic
(hypotension, Tachycardia, hypophysitis:
hyponatremia) Idiopathic condition,
• Investigation: mainly associated
– CT / MRI: huge with pregnancy (3rd
mass in sella with trimester), IgG4 disease
intralesional density & iplimumab also cause
(haemorrhage) Q
pituitary insufficiency .
• Treatment: IV fluids & It is associated with
hydrocorticosteroids ACTH > TSH deficiency.
(Dexamethasone / Treatment - Steroids
Methylprednisolone) • To differentiate between
lymphocytic hypophysitis
& pituitary adenoma,
we should check stalk
thickness, bulky pituitary
(symmetric enlargement
in Lymphocytic
hypophysitis)
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Medicine

PITUITARY ADENOMA • >200 → confirms the prolactinoma

• Associated with Hyper prolactinemia

Other causes
• Drugs
– D2 receptor blockers: Anti emetic →
metaclopramide, domperidone
– Anti psychotic: haloperidol, risperidone
– Amine depletors: tetrabenazine, verapamil
Classification based on size & functional
status • CKD

1. Size • Focal seizures

• <1 cm: Microadenoma • Stress
• >1 cm: Macroadenoma
• Pregnancy/ Post partum periods
• Macroadenoma lead to VFD (mainly bitemporal
Heminopia), headache, diplopia, cranial nerve • Anything that stimulates the reflex arch
palsy
• Primary hypothyroidism
2. Functional status
• Idiopathic
• Functioning tumor: prolactinoma
• Non functioning tumor: gonadotropin adenoma Clinical features
– Most common pituitary adenoma overall:
• Most common: Gonadal dysfunction
prolactinoma
– 2nd Most common: Gonadotropin adenoma – Prolactinemia → decrease gonadotrophs →
decrease FSH, LH → Hypogonadotrophic
– 3rd Most common: Somatotroph adenoema
hypogonadism
– 4th Most common: ACTH secreting pituitary
adenoma / corticotroph adenoma • Common in females → present with infertility
– Least common: Thyrotroph adenoma → cause • 2nd Most common feature: galactorrhea
central hyperthyroidism

Investigation Indications for treatment

• Dynamic contrast enhanced MRI • Any Symptomatic adenoma (micro / macro)
• Macroadenoma: Seen as figure of 8 or snowman • Macroadenoma (with or without symptoms)
appearance
Treatment
PROLACTINOMA – Dopamine receptor agonist (bromocriptine
• Normal Prolactin <20 → in case of females desiring pregnancy
or already pregnant, cabergoline → in
• >20 = suspect prolactinoma
case of non pregnant female, pergolide

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→ have impact on heart valves so annual

echocardiogram is mandatory
Q

• 2nd line treatment: trans sphenoidal surgery

• 3rd line treatment: pituitary radiotherapy

• If patient have infertility then start

bromocriptine
check prolactin levels after 3-6 months → if normal,
then female can conceive → if it is not normal, then
do trans sphenoidal surgery or radiotherapy

If patient conceives, then stop bromocriptine &

assess headache, visual field defect etc.
Clinical features
↓ • Bony changes (hypertrophy) → skull - frontal
If patient have stable tumor → just observe bossing, enlargement of mandible & maxilla,
enlarge frontal sinus seen in X-ray
↓
• Soft tissue changes → results in obstructive
If unstable tumor & have symptoms like headache, sleep apnoea, increased ring size and shoes size,
VFD widening of joints, spade-shaped distal phalanx
↓

Do MRI → if enlarged mass present → start

bromocriptine

Increased heel pad thickness > 23-25 mm

Q
If treatment effective, If treatment fails, •
continue bromocriptine do surgery (TSS), • Metabolic changes → Impaired glucose
tolerance, DM
ACROMEGALY • Hyperhydrosis → hypertrophy of sweat glands
- Earliest sign
• Due excess of Growth hormone in adults
• Patient may also have LVH, cardiomegaly,
• Most common cause of GH excess in acromegaly thyromegaly & renomegaly, colonic polyp -
is somatotroph adenoma (among them 40% have increase risk of colonic cancer
GS alpha mutation)

• Very rarely, patient have Hypothalamus

hamartoma, ectopic tumors like small cell
Lung tumor, medullary cancer, pancreatic
neuroendocrine tumors that leads to excess GH

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Medicine

Investigation • Ends up with permanent Central DI

Serum IGF -1 → screening test Hook effect

Q
•

Patient have functioning macro adenoma

Q
•

if normal, then if value is increased, • Assay → normal or mild increase in prolactin

level → dilute the sample (1:100) → if value is
rule out GH excess do 75 gm of OGTT
normal or mildly increased, the dilution will be
undetectable

If decreased, then rule if GH increases, then it • If the value is detectable / increased, then it is
known as hook effect
Out GH excess confirms GH excess

• To localize, do dynamic contrast enhanced MRI Macroprolactin

• Mass in pituitary confirms somatotroph adenoma • They bound to immunoglobulin segments,
mainly IgG
• If no mass seen in MRI, then cause would be
ectopic • Assays: Higher prolactin values
• Investigation of choice: PEG precipitation
Treatment (polyethylene glycol)
Q

• 1st line treatment: trans sphenoidal surgery

• 2nd line: medical treatment
SIADH (SYNDROME OF
INAPPROPRIATE ANTIDIURETIC
– Somatostatin receptor agonist (2 & 5):
Octreotide, Lanreotide, Pasireotide HORMONE)
– GH receptor antagonist: Pegvisomant
Q
• Have ADH excess / increase ADH effect

– Pituitary radiotherapy • Most common cause is hyponatremia in

hospitalized patients
Stalk effect
Clinical features
• If we transect the stalk, there will be deficiency
of all pituitary hormones except prolactin - it • Euvolemia (normal JVP & BP, no Ascites &
increases because it is controlled by Dopamine edema, no Pleural effusion)

• Non functioning macro adenoma can compress
the pituitary stalk which can produce
hyperprolactinemia
• Trans sphenoidal surgery also does the stalk
transection
• Leads to classic triphasic response
• Hyperosmolar hyponatremia (decrease serum
osmolality)
• Increased urine osmolality
Treatment
• Check if severe symptoms (coma, seizures)
present, give 3% NaCl → if no severe symptoms,
do standard SIADH management
Q

• Most commonly after TSS, patient have

Transient central DI (treatment of choice = • To reduce total body fluid, restrict water (1-
desmopresssin) lasts for 1-2 weeks, then there 1.5 L/day water is sufficient) → to increase
will be degeneration of neurons of posterior effect, patient can use strongest drug Vaptans
- tolvaptan (hepatotoxic), conivaptan (aquaretic
pituitary → release the stored SIADH →
agent) → increase urine excretion
results in Transient SIADH
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Etiology – History of subarachnoid haemorrhage,

polyuria
• Tumor: small cell lung cancer
• Treatment: IV fluids (0.9% NS)
• Pulmonary causes: pneumonia (mainly legionella
infection), TB, PPV
Approach to polyuria
• Neurological: GBS
• >3 L/day or >2 L / m2 / Day or 40 ml / kg / day
• Drugs: anti cancer drugs (cisplatin, vincristine,
Cyclophosphamide), antidepressants, • If UOSM decreased→ water diuresis → seen in
DI, 1° polydypsia
Q
antipsychotics, anti epileptics (carbamazepine,
oxcarbamazepine), clorpropamide, thiazide
• Endocrine patients

Differential diagnosis
• Cerebral salt wasting syndrome
– Defect of CNS → increased release of BNP,
increased urinary sodium & osmolality
– Total body salt decreases → patient will be
Hypovolemic

Conditions S. Na+ Baseline Post H2O Post dDAVP Pituitary MRI Baseline AVP
UOSM deprivation
PP N/↓ ↓ ↑ Same N N/↑
CDI N/↑ ↓ Same ↑ Stalk thickening ↓↓
NDI N/↑ ↓ Same Same N N/↑

Treatment of choice for CDI - ƒ Post neuro surgery

Desmopresssin ƒ Any CNS infections
• Causes of CDI
– Congenital
Treatment of choice for NDI -
thiazide
ƒ Didmoad syndrome / wolfram syndrome
Q

• Causes of NDI
is mitochondrial transmitted disease
ƒ DI - Diabetes insipidus – Congenital

ƒ DM - Diabetes mellitus ƒ Due to vasopressin 2 receptor mutation

ƒ OA - Optic atrophy ƒ Male > female

ƒ Aquaporin 2 mutation, AR pattern
Q
ƒ D - Deafness
– Acquired – Acquired
ƒ Infiltrative cause ƒ Drugs-related Causes: Lithium,
ƒ Metastasis demeclocycline, Amphotericin B

ƒ CNS causes
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ƒ Electrolytes problems: ↑ Ca2+, ↓ K+

ƒ Other: Sarcoidosis, amyloidosis, multiple myeloma, sickle cell disease

MEN SYNDROMES
MEN 1
Features MEN 2A (Sipple) MEN 2B MEN 4
(Wermer)
Inheritance AD, Chromosome 11 AD, chromosome 10 AD, Chromosome 10 AD
RET gene (proto onco Q
MEN 1 (menin Q RET gene
gene)
Mutations protein – tumor • Codon: 918 (worst CDK N1B
Q • Codon Mutations: 634,
suppressor protein) mutation)
88
Present, cause
PHPT + - +
hypercalcemia
present, MC is
Pituitary adenoma - - +
prolactinoma
present, non
functioning >
Pancreatic NENs gastrinoma - - +
• Most common
cause of death
present, most
common cause
MTC - +
of death, most
aggressive
Present, Bilateral &
Pheochromocytoma - Present, Bilateral & benign
benign
Familial medullary thyroid
Angiofibroma, Reproductive organ
cancer, Hirschsprung Mucosal neuroma,
Others lipoma, foregut tumors: Testicular
disease, cutaneous lichen marfanoid habitus
Carcinoid tumor
amyloidosis
≥ 2 major features
present or 1 major
2 major manifestations
feature with FDR
Diagnosis or FDR with proven RET Same as MEN 2A
with MEN 1 or
mutation
positive MEN 1
gene mutation
In 634, 883 mutation:
do Total thyroidectomy In 918 Mutation: do
Treatment before 5 years of age in Total thyroidectomy
case of intermediate to within 1 year of age
high risk of Mutations

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IPEX (immune poly endocrinopathy X

linked):
• FOX P3 Mutation

(IBD, Ulcerative colitis)

DIABETES MELLITUS -
DIAGNOSIS
APS (AUTOIMMUNE
Normal Pre-diabetes DM
POLYGLANDULAR SYNDROME)
FPG (mg/dl) < 100 100 – 125 ≥ 126

APS Type 1 2h PG (mg/dl) < 140 140 – 199 ≥ 200

• Rare HbA1C (%) < 5.7 % 5.7 – 6.4 % ≥ 6.5 %

Classic symptoms of diabetes + random blood sugar
Mutation: AIRE gene
Q
•
≥ 200 → DM
• APS 1 also known as Autoimmune poly
endocrinopathy with candidiasis & ectodermal Types of DM
dystrophy
1. Type I DM
• Characteristic triad
• Due to Ab like IAA (insulin auto Ab), ICA (islet
cell Ab), Zn8T8 (zinc transporter Ab), GADA
(anti CAD 65) → cause beta cell destruction
Q

• Features:
– Osmotic symptoms: polyuria, polydipsia
• Ectodermal dystrophy
– Catabolic symptoms: weight loss
APS Type 2 – Age of onset: juvenile
• Female > male • Treatment
• Polygenic inheritance – Insulin
• Triad

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2. Type II DM Diabetes Mellitus - Management

• Most common in adults, now common in children Effect Drugs

also Insulin, insulin secretagogues,

Hypoglycemia risk
sulphonylurea, meglitinides
• Features: • Weight loss: SGLT 2 inhibitor,
GLP 1 receptor gonist
– Metabolic symptoms
• Normal: metformin, alpha
– Obesity Weight glucosidase inhibitor, DPP4
inhibitor
– PCOS
• Weight gain: sulphonylurea,
– Acanthosis nigricans meglitinides
• Treatment • Reduced by SGLT 2 inhibitors,
MACE GLP 1 agonist
– Oral drugs mainly +/- insulin
• Induced by rosiglitasone

3. MODY (Maturity onset diabetes in young Reduce heart failure: SGLT 2

inhibitors
= age <25) HF Induce heart failure event: DPP4
inhibitors (saxagliptin / alogliptin),
• Monogenic, AD pattern
Pioglitazone
• Strong family history DKD SGLT 2 inhibitors, GLP 1 agonist
Safe in ESRO Linagliptin & pioglitazone
• Beta cell dysfunction → decrease release of
Metformin, incretin drugs, DPP4
insulin
GI side effects inhibitors, GLP 1 agonist, alpha
• Most common is MODY type 3 → HNF 1 alpha glucosidase inhibitor

gene mutation Incretin group of drugs (DPP4

Pancreatitis
inhibitors & GLP 1 agonist)
• Treatment: sulphonylurea • Pioglitazone

• MODY type 2 is least severe • Increase risk of Bladder cancer

Cancers
(GLP 1 agonist increases risk of
• Weight of latent is normal medullary & pancreatic cancer
Osteoporosis (by pioglitazone),
4. LADA (latent Autoimmune diabetes in Bone issues
Canagliflozin
adults) • NAFLD & NASH: metformin,
Q

• Most common in age of > 30 pioglitazone

Non DM uses
• Late dumping syndrome reduced
• Type 2 diabetes with Ab by acarbose - liraglutide
Most common anti body is anti GAD Ab
Q
•

• NIDDM is maintained atleast till >6 months,

then it is converted into IDDM

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Effect Drugs Types of insulin

• Bromocriptine, Bile acid • Rapid acting insulin:
sequesters
– Analogs: lispro, aspart, glulisine
– Colesevelam, renolazine
– Saroglitazar: dual PPA alpha – Short acting: regular insulin → cheapest and
Q
& gamma agonist easy to use, IV
Misc drugs used
– Teduglutide: GLP 2 agonist,
in DM ƒ Analogs & short acting are Prandial insulin
→ decreases intestinal
motility ƒ Given before meal
– Dapiglutide: GLP 1 & 2 agonist
• Intermediate acting: NPH
– Tirzepetide: Max. weight loss
Long acting: Glargine, detemir, degludec
Q
→ GLP 1 & GIP analogue •
– Intermediate & long acting are used as Basal
Complications of diabetes insulin
• Vascular diseases – Given irrespective of meal time
– Micro
• Insulin Given subcutaneously in
ƒ Retinopathy
– Abdomen
ƒ Neuropathy
– Lateral thigh
ƒ Nephropathy
– Posterior arm
ƒ DKD
• Never Given on buttocks
– Macro
ƒ Coronary artery disease • Site should be rotated every time otherwise it
can lead to lipodystrophy
ƒ Peripheral artery disease
• Complications
ƒ Cerebral artery disease
– Hypoglycemia
• Infections
• Cataract: Due to excessive sorbitol production
Q – Weight gain

• Glaucoma – IV insulin → hypokalemia

– Subcutaneous insulin → lipodystrophy, lipo
Effects of insulin
atrophy
Features Dawn effect Somogyi Insulin def.
effect DKA vs HHS
7 am glucose ↑ ↑ ↑
DKA HHS
3 am glucose N ↓ ↑
Blood Glucose 250 – 400 mg% >600- 800 mg%
Treatment ↑ ↓ ↑
Comorbidities Less More
• Dawn effect: Natural increase in counter Coma / surgery Less More
regulatory hormone
-/ may little
Plasma ketone ++++
• Somogyi effect: Mid night Hypoglycemia & present
early morning hyperglycemia S. HCO3 <18 mmol/L >18 mmol/ L
• Insulin def.: Night dose of insulin is not Arterial pH <7.3 >7.3
sufficient → effect seen as hyperglycemia in Normal ( < 12 –
morning AG ↑ ( >12-14)
14)

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DKA HHS (Bevacizumab, Ranibizumab)

S. Osm ↑↑ ↑↑↑(>320 osm/L) – Indication for PRP
Sodium 125 -135 135-145 ƒ Severe non proliferative diabetic Retinopathy
Potassium N/ ↑ N
ƒ Proliferative diabetic Retinopathy
Creatinine N/ ↑ ↑↑
Mortality <1% 15%
ƒ Vitrectomy: for vitreous haemorrhage

• In DKA, plasma ketone is detected best by ƒ VEGF: for diabetic retinal edema
Beta hydroxy butyrate level → >30 mmol /L
Diabetic neuropathy
• In HHS, beta hydroxy butyrate is <1.5 mmol / L
• Distal symmetric polyneuropathy
• Treatment
– Length dependent atonal neuropathy
– DKA
– Earliest site involved: feet
ƒ FLIP : Fluid (in 1st 3 hours → 2-3 L or
10-20 ml / kg/ hr of NS 0.09% → After – Painful but 70% painless, burning, numbness
3 hours shift the fluid to 0.45% NaCl), – Treatment for painful form: SNRI, tricyclic
Insulin, potassium
Q
antidepressants, calcium channel blockers
ƒ If capillary blood glucose value is <200- • Diabetic autonomic neuropathy
250 mg/dl → add Dextrose 5% solution
to prevent Hypoglycemia – GI (bladder & bowel problems: constipation,
diabetic diarrhea, gastroparesis), GU
– Use FDII regime (erectile dysfunction), CVS (Tachycardia)
ƒ If S. Potassium: problems

1. 3.3–5.2 - give insulin + IV fluid + KCl • Diabetic amyotrophy

2. <3.3 - give KCl → when K+ gets normal → – Asymmetric involvement

give insulin – Focal pain in hip, thigh, buttock
3. >5.2 → insulin + close watch potassium – Proximal weakness because of radial & nerve
– S. PO42- <1 mg/dl → risk of rhabdomyolysis root involvement in diabetes

ƒ If pH is <7 → add IV NaHCO3 • Mononeuropathy

– Can affect the peripheral nerves
Microvascular Complications of
ƒ Most common: Median nerve (carpal tunnel
diabetes syndrome)
• Non proliferative diabetic Retinopathy
ƒ Common fibular nerve: foot drop
– Micro retinal Aneurysm
– Can affect the central nerves
– Hot spot
ƒ Most common: CN 3 > 6 > 4
– Cotton wool spot
ƒ CN 3 palsy + Pupil sparing = Diabetes
• Proliferative diabetic Retinopathy
– Neovascularization near the disc
Q Diabetic nephropathy
• Check Microalbuminuria → proteinuria → GFR
– Treatment: Pan retinal photo coagulation
drop → end stage kidney disease
Q

+/- vitrectomy + intra vitreal anti VEGF

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• Biopsy: Kimmelstiel Wilson lesion also known as – Beta hydroxy butyrate <2.7 → not insulin
nodular glomerulosclerosis mediated
• Treatment: <2.7
– ACE inhibitors or ARB blockers
– Finerenone: non steroidal MRA if insulin value <3 → cause is IGF 2

>3
When to start screening for diabetes
• Type 2 diabetes: at the time of diagnosis C peptide <0.2 → exogenous insulin abuse
• Type 1 diabetes: after 5 years of diagnosis, >0.2
then start screening
• Retinopathy: do fundus examination Rule out sulphonylurea abuse → if positive,
• Nephropathy: do EGFR + urine albumin: it is an induced cause
creatinine If -ve
• Neuropathy: do 10 gm mono filament testing
+ deep tendon reflexes + pain & temperature Do Imaging
assessment
• Check for Type 2 diabetes:
• If screening is normal → do annual screening
– MRI of pancreas → mass lesion present →
METABOLIC SYNDROME due to insulin
• Criteria
Q
– If MRI is normal, do Ab testing because
insulin auto Ab can cause Hypoglycemia
I. Central obesity - check by waist → do SACST (selective arterial calcium
circumference stimulation test to diagnose Nesidioblastosis
ƒ Males ≥ 102 cm, females ≥ 88 cm (benign beta cell hyperplasia) - can be
Idiopathic (known as NIPHS – non insulinoma
ƒ In Asian males ≥ 90, females ≥ 80
pancreatogenous Hypoglycemia syndrome)
II. Impaired fasting glucose, Impaired glucose or occur after gastric bypass)
tolerance, frank Type 2 diabetes
Whipple’s traid
Q

III. Hypertension •
Symptoms of Hypoglycemia
IV. Triglyceride ≥150 mg/dl
– Low HDL: males <40, females <50
• If any 3 of these 5 Criterias are present, it is
diagnosed as Metabolic syndrome

APPROACH TO HYPOGLYCEMIA
• Check for diabetes
– Present: Most common cause is drugs - Documentation of Complete resolution
insulin, sulphonylurea, pioglitazone
Q
Hypoglycemia of symptoms with
glucose
– Absent: Do 72 hour fast (CBG <45 – take
blood sample – end the fast)

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• Level 1: ≤ 70 mg/dl Any 1 is positive

• Level 2: ≤ 54 mg/dl
• Level 3: incapacitated Endogenous cortisol excess → endogenous
Cushing syndrome
CUSHING SYNDROME
• Excess cortisol Level True Cushing Pseudo Cushing
• Most common cause: exogenous corticosteroid • Conditions associated with pseudo Cushing
use syndrome:
• Clinical features: – Severe depression
– Weight gain (centripetal obesity)
– Severe obesity
– Round or moon face
– Critical illness
– Dorso cervical fat pads / Buffalo hump
– Clinical alcoholic patient
– Purple striae (due to spontaneous bruising)
• After resolution of these symptoms, test CRH
– Proximal myopathy stimulation after dexamethasone suppression
Q

– Metabolic disturbances: – If the test is negative → pseudo Cushing

ƒ Hyperglycemia
– If test is positive → true Cushing
ƒ Hypokalemia
• True Cushing
ƒ Hypertension low = source is Adrenal → CT /
S. ACTH MRI
ƒ hirsutism
ƒ Fungal infections (ex: candidiasis) Normal / High = source is
pituitary/ ectopic (Pituitary
ƒ Cataract adenoma = cushing’s disease)
ƒ Nephrolithiasis
ƒ Polyuria – Difference between Pituitary vs ectopic
source
ƒ Psychosis, depression, dementia
ƒ Use high dose dexamethasone test or
– Blood changes: neutrophilia, eosinopenia, CRH stimulation test
lymphopenia
ƒ If there is response = problem is pituitary
– Facial plethora adenoma
• Work up:
– 3 am cortisol level check → if low → exogenous
Cushing disease Do MRI → mass present → Cushing disease
If normal / increased ƒ If not response = ectopic ACTH production

Do screening → low dose dexamethasone

suppression test, 24 hour urinary free Do CECT abdomen → mass present → ectopic
cortisol, late night salivary cortisol source
ƒ If Imaging is normal → do Bilateral IPSS
(inferior petrosal sinus sampling)
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ADRENAL INSUFFICIENCY • Work up

A.1° insufficiency
• Problem with adrenal gland
• Low cortisol production → increased ACTH
• Most common cause in India - infectious,
leprosy, in western world – Autoimmune
adrenalitis
Q

• Low level of adrenal Androgen → so low level of

DHEAS
• Low aldosterone level results in salt wasting →
Hypovolemic hyponatremia PHEOCHROMOCYTOMA
• Treatment: hydrocortisone, fludrocortisone • Tumor of chromatin cells

B. 2° insufficiency • Type of paraganglioma

• Problem with Pituitary gland • Most common site is Adrenal gland (in medulla)
• Low level of ACTH → low S. Cortisol • Most common extra Adrenal site is Para Aortic
region near the organ of zuckerkandl
Q
• Lead to Risk of Adrenal crisis
• Low Adrenal Androgen • Genetic syndromes associated:
• Aldosterone level normal – MEN 2A, 2B
• No salt wasting → euvolemic hyponatremia – VHL
• No hyperkalemia, no Metabolic acidosis
– NF-1
• Investigation of choice: ACTH stimulation test
– TMEN 127
• Non sun exposed area are quite specific for this
disease features (gingiva, nails, nipples) – SDH

• Clinical features: – MAX

– Weakness & fatigue • Biopsy: histopathology
– GI symptoms, abdominal discomfort
– Neutropenia, eosinophilia, lymphocytosis

– Zellballen pattern: nest of tumor cells

surrounded by supporting cells known as
sustentacular cells
Q

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– By giving alpha blockers → phenoxybenzamine

Q

• Clinical features: 6 P’s

– Pressure (BP) - paroxysmal hypertension or – After 24 hours, give beta blockers →
sustained hypertension propranolol

– Palpitation – Liberal use of salt & fluid

– Pain – headache, chest pain (most common • Surgery

cause of death) – Increased BP → treat with NTP
– Pallor due to vaso constriction – Tumor removed → hypotension → manage by
– Perspiration IV fluids

– Postural hypotension – If metastasis present, treatment will

continue for that even after removing tumor
– Weight loss
ƒ Most common site for Metastasis → liver
– Hyperglycinemia
ƒ Best treatment → I131 MIBG
– Constipation
Congenital Adrenal hyperplasia
– Hypercalcemia
• AR inheritance
• Low cortisol, high ACTH - reason for
hyperpigmentation
Q

• 21-hydroxylase deficiency, 11-OH deficiency,

17-OH deficiency, 3-beta-hydroxy steroid
deficiency
• Work up
• 21 & 11 OH-deficiency affects Adrenal gland
– Urinary Metanephrines test - elevation is
specific for chromaffin cells
Q
• 17 OH & 3 beta hydroxy Steroid deficiency
affects Adrenal & gonads
– Plasma metanephrines test - preferred only
in high risk patients
Q
• In 21 & 11-OH deficiency, female child will
have ambiguous genitalia → excess Androgen
– If test value is mildly increased → it is false
from Adrenal glands
positive due to some drugs reaction like
alpha, beta blockers, diuretics etc. • In 17-OH deficiency, male child will have
ambiguous genitalia
– If significant elevation in value → do imaging
of abdomen > chest • In 3-beta hydroxy steroid deficiency, both
ƒ Normal imaging, no mass - can be false male & female children will have ambiguous
positive genitalia

ƒ Abnormal imaging, mass present → • In 17-OH & 3-BHS deficiency, there will be
Pheochromocytoma decreased Testicular Androgen

For metastatic & multifocal disease • 21-OH deficiency is also known as non classic
congenital Adrenal hyperplasia
• Nuclear imaging: I123 MIBG, PET scan, Ga68
(DOTATOC / DOTATATE scan) – Post puberty → PCOS-like presentation
→ hyperandrogenism features, oligo /
• Preparation: reduce BP → target <160 /90
amenorrhea
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– Treatment: hydrocortisone or Prednisolone ƒ Treatment: Conservative

– Prenatal Treatment: dexamethasone
Q
– With high T4 → central hyperthyroidism
ƒ Continue Treatment if karyotype is 46xx • High TSH
+ recessive defect till delivery
– With low T4 → 1° hypothyroidism
ƒ Stop Treatment if karyotype is 46xy + no
recessive defect ƒ Treatment: T4 replacement
Integrated approach to TFTs & Thyroid – With normal T4 → subclinical hypothyroidism
disorders
ƒ Treatment - T4 replacement
• Low TSH & T4 → Central hypothyroidism
• Etiology: 2° pituitary > 3° Hypothalamus cause ƒ Indication: TSH >10, symptoms present

• High T3, Normal T4 - Isolated T3 toxicosis – With high T4 - central hyperthyroidism

• Normal T3 & T4 - Sub-Clinical hyperthyroidism – Dose of T4 replacement therapy:
• TSH low, T4 high - 1° hyperthyroidism
ƒ 1.5 – 1.7 mg / kg / day
• Radioactive iodine ablation: I123 → t1/2 = 13
hours ƒ Better to give levothyroxine at empty
stomach
• Alternatively, we can use Tc99m pertechnetate
→ t1/2 = 6 hours ƒ Starting dose - 100 kg/day
• Diffuse increased uptake of thyroid: Grave’s
ƒ Check TSH every 6-8 weeks
disease → TRAG Ab test should be done to
confirm • Most common cause of hypothyroidism in world
is Autoimmune thyroiditis (Hashimoto’s)
Q
• Patchy increased uptake:
– Focal: Solitary toxic adenoma • Risk of Malignancy with cold nodules is highest
– Multiple: Toxic multinodular goiter (plummer’s
disease)
Q

• Thyroglobulin
– Low level - Source is exogenous - Factitious
hyperthyroidism
Q

– High level - source is endogenous- thyroiditis,

also from ovarian tumor (do abdominal USG)
• Normal TSH
– With low T4 - central hypothyroidism
– With normal T4 → look for T3
ƒ Low T3 → low T3 syndrome or sick
euthyroid syndrome

ƒ In early stage of this syndrome: Low T3,

reverse T3 is high, T4 & TSH is normal

ƒ In late stage: Low T3, high revers T3, low

T4 & TSH
* For Making Notes
 59
Medicine

Graves disease – Moderate to severe: corticosteroid ,

Teprotumumab
• Type 2 hypersensitivity reaction mediated by
TRAB antibody
Q
– Surgical decompensation of orbit
• Example of autoimmune thyroiditis • Most specific investigation is Ab detection test
• Clinical features • Doppler shows excessive vascularity
– Thyrotoxicosis (high T3 & T4 + low TSH)
Treatment of hyperthyroidism
– Euthyroid profile (normal TFT) also present
in some patient • For child & pregnant female: anterior thyroid
drugs
– Tachycardia
– 1st line: PTU - less teratogenic
– Palpitations
– 2nd & 3rd line: methimazole - teratogenic,
– Systolic hypertension
aplacia cutis
– High pulse pressure
– Non pregnant females: Beta blockers & anti
– Diarrhea thyroid drugs (methimazole > carbimazole),
– Menstrual irregularity CCB
– Thyroid eye signs – Continue till euthyroid levels
– Extra thyroidal Clinical features – Definitive Treatment: Radio iodine ablation -
ƒ Graves orbitopathy (mostly asymmetrical) I131 = t 1/2 = 8 days
Q

→ orbital fibroblast → exophthalmos

ƒ Contraindicated in pregnancy, breast
→ exposure keratitis → Corneal ulcer &
blindness, leads to edema, Restrictive feeding mother, suspecting cancer,
extra ocular myopathy (most common is moderate to severe orbitopathy
inferior Rectus muscle)
Q

Thyroid Storm
ƒ Dermopathy (pre tibial myxedema)
• Most common cause is inadequate preparation
ƒ Acropachy (bone disease - rare)
of gland for surgery
• Clinical features
– Undetectable TSH, detectable T3, T4
– Increased HR
– Increased systolic BP
• Treatment
– Beta blockers (esmolol, metaprolol, propranolol),
• Investigation
CCB (verapamil, diltiazem), anti thyroid
– IOC: MRI of orbit drugs (PTU), lugol’s iodine/potassium iodine,
dexamethsone, plasma exchange
• Treatment
Myxoedema coma Q

– Mild to moderate disease: conservative

• Hypothermia

* For Making Notes

60
Cerebellum Quick Revision Notes

• Reduced mentation • Very high TSH, very low T4

• Bradycardia, bradypnea • Treatment:
• Hypotension – IV / oral T4
• Hypoglycemia – Hydrocortisone

THYROIDITIS
Chronic Subacute Subacute
Features Acute suppurative Riedal’s
lymphocytic lymphocytic granulomatous
Autoimmune,
Etiology HLA DR 3, Autoimmune Viral Infection -
DR5, B8
Pain - - ++ ++ -
Fever /
- - ++ ++ -
malaise
1° Hypothyroid to
TFT Thyrotoxicosis N TFT N TFT
hyperthyroid euthyroid
Persistence Yes Variable No No Yes
Lymphocytic Lymphocytic Giant cells & Fibrosis +
Pathology Abscess
infiltration infiltration granulomas seen inflammation
Beta blockers,
Antibiotics, incision Immuno suppressent
Treatment Levothyroxine NSAIDS,
& drainage (tamoxifen), surgery
corticosteroids

• Presence of germinal centres indicate chronicity. • Hashimoto patients are at increased risk of PTC
& Thyroid lymphoma
• Presence of Hurthle cells is common in
Hashimoto’s (but not specific).

Calcium & bone disorders

Hypercalcemic Disorder
Disorder Ca PO4 PTH ALP Comments
PHPT ↑ ↓ ↑↑ ↑ • Asymptomatic, picked incidentally, renal stones, abdominal pain
• Most common cause: parathyroid adenoma (right inferior
parathyroid gland involves most commonly)
• Less common cause: hyperplasia, carcinoma
Q
• Diagnosis: Tc99m sestamibi scan
• Treatment: Surgery in case of >65 years age, severe
hypercalcemia, low bone mineral density
• If no surgery then give cinacalcet
FHH ↑ ↓ ↑ ↑ Calcium sensing defect, asymptomatic, benign
PTHrP ↑ ↓ ↓ ↑ Most common mechanism of hypercalcemia in Malignancy, renal cell
cancer
Lyrics mets ↑ ↑ ↓ N Multiple myeloma, activate osteoclast
* For Making Notes
Vit D toxicity ↑ ↑ ↓ Variable Marker: 25 HCC value
Sarcoidosis ↑ ↑ ↓ Variable Lymphadenopathy, lymphomas, 25 HCC & 1, 25 HCC level increases
• Treatment: Corticosteroid
 61
Medicine

Other causes of hypercalcemia – Severe dehydration, shock, low BP, Tachycardia

• Thiazide – Altered mental status

• Endocrine conditions such as hyperthyroidism, – Weakness

Adrenal insufficiency – Lethargy
• Vitamin A toxicity • ECG changes: ST elevation, short QT, J waves
• Milk alkali syndrome - chronic form is known as • Treatment:
Burnett syndrome
– Correct shock by normal saline
• 3° Hyperparathyroidism
– Reduce S. Calcium → by calcitonin ,
Hypercalcemia Bisphosphonates (IV pamidronate ,
zolendronate)
Q

• Other:
– Loop diuretics only in case of hyper volemic
state
Milk alkalosis AKI
– Dexamethasone in case of vit D excess
Hypercalcemic crisis – Denosumab → subcutaneously, safe in renal
failure
• Clinical features
– Dialysis
– Severe polyuria
Hypocalcemic disorders
Disorders Ca PO4 PTH ALP Comments
Q
Cause: Autoimmune , APS 1, post thyroid surgery – have
1° Hypoparathyroidism ↓ ↑ ↓↓ N Transient hyperparathyroidism, post parathyroidectomy
(rare), Wilson disease, Hemochromatosis
• Rickets, osteomalacia, cod fish vertebrae, looser’s zone
In diet↓ / pseudo fractures
Vit D deficiency ↓ ↑ N /↑
In CKD↑ • Elevated ALP in CKD → renal osteo dystrophy → rueger
jersey
• IA, Ib , Ic, II → IA & Ic have skeletal defect called as
Albright hereditary osteo dystrophy
PHP (GNAS gene #) ↓ ↑ ↑↑ N
• Features: Short stature, round face, brachydactyly
Q
(knuckle Dimple sign)
PPHP (GNAS gene #) N N N N Albright hereditary osteo dystrophy
• High bone turnover
• X-ray: cystic & blastic lesion
• Abnormal bone remodelling
• If symptoms present: bone pain (tibia)
PDB N N N ↑↑
• MC neurological symptoms: headache
• CN affected commonly: 8th CN
• Increased risk of osteosarcoma (giant cell tumor of bone)
• Treatment in Symptomatic patient: Bisphosphonates
Osteoporosis N N N * ForNMaking
BoneNotes
metric problem, trabecular bone affected
62
Cerebellum Quick Revision Notes

– -1 to -2.5 = osteopenia → do therapy >

Other causes of hypocalcemia
decide by FRAX tool (tells about 10-years
• Critical illness risk of any major fracture & hip fracture)
• Excessive bone turnover (post parathyroidectomy) – < - 2.5 = osteoporosis - do treatment
• If patient is heavily immobilized- paget’s disease
Approach
• Sequestration (high PO4, excess citrate, • History of fragility fracture ( colle’s fracture )
pancreatitis, alkalosis, Bisphosphonates)
• Check if Kyphosis is present or not
Clinical features • History of wedge compression fracture
• Neuromuscular Irritability (perinoral parasthesia, • If patient does not have history of fragility
Chvostek sign, Trousseau sign, tetany, seizures) fracture → do BMT screen - DXA scan
• Target for screening: Elder patient (>65 years
• Cardiac irritation
age) or <65 years of age + risk factors present
ECG: ST depression, long QT
Q
• • Risk factors:
Treatment – Advancing age
– Glucocorticoids use
• If patient have severe symptoms: IV calcium
gluconate – Personal history of fracture after 40 years
of age
Diagnosis & management of post – Family history of hip fracture
menopausal osteoporosis – Active Smoking
– Excess alcohol consumption
Diagnosis
– Malabsorptive state
• Bone mineral density
– Chronic liver disease
• DEXA scan - check T score – Rheumatoid arthritis
– > -1 = normal - no treatment require , take – IBD
vitamin supplements (800 units of vitamin
D / day) – Early menopause

* For Making Notes

 63
Medicine

Treatment • MRKH: Patient have low testosterone level,

female patient, pubic & axillary hair present, no
1st line = Bisphosphonates
Q
• palpable gonads
– Oral: arendronate, risedronate • Complete AIS: Testosterone high, male patient,
ƒ Side effect: pill-induced esoohagitis pubic & axillary hair absent, palpable gonads

ƒ Contraindication: GERD • If Uterus is present

– IV: zolendronate • Breast development present

ƒ Side effect: hypocalcemia, osteonecrosis • For outflow tract obstruction, do MRI → if

of jaw, atypical femoral fracture, present → vagainal atresia, Transverse vaginal
nephrotoxic
Q
septum, imperforate hymen

• 2nd line = anabolic agents - teriparatide, • If no outflow obstruction → constitutional delay

abaloparatide, anti sclerostin (romosuzumab) puberty, Hyper androgenic states (early PCOS,
non classic Adrenal hyperplasia), prolactinoma
• Denosumab: subcutaneous
• If Secondary sexual characteristics are absent:
• SERM: raloxifene (hot flushes risk present) -
only give if high breast cancer risk present – Look at the height of patient

• Bazedoxifene - with Conjugated estrogen ƒ Short: look FSH → if low - central causes

• Hormone replacement therapy: estrogen ○ High FSH - Turner syndrome

– Oral ○ MCC of 1° amenorrhea - Turner

syndrome
– Transdermal patch
ƒ Normal:
Approach to primary amenorrhea ○ Low FSH: Isolated gonadotropin
• No menstruation till Age ≥ 15 years or > 5 years deficiency-kalmman syndrome
of breast development ○ High FSH: Gonadal dysgenesis
• Look for the uterus first → if absent, do
karyotype
– 46xx (+) → MRKS
– 46xy → CAIS

* For Making Notes

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PITUITARY HYPOTHALAMIC SYSTEM
Anterior Pituitary
Growth Hormone [GH]
Thyroid Stimulating Hormone
Adreno corticotropic Hormone
Chapter - 6 Endocrine system
Hypothalamic control
GHRH [GH Releasing Hormone]
GHIH [GH Inhibiting Hormone]
Thyrotropin Releasing Hormone
Corticotropin Releasing Hormone
Uses of Dopamine AgonistsQ
Dopamin - Diabetes mellitus type 2 (Bromocriptine)
Agonists - Acromegaly (by decreasing GH)
Suppress - Suppression of lactation.
Plasma - Parkinsonism (Bromocriptine can be used)
Prolactin - Hyperprolactinemia

Gonadotropins GnRH [Gn Releasing Hormone] Drugs for Acromegaly

Prolactin Prolactin Inhibiting Hormone A. Decreased GH release

1. Growth Hormone Inhibiting Hormones [GHIH] – Octreotide

– It is also known as Somatostatin – Cabergoline

SOMA TOSTATIN USESQ – Bromocriptine

S → Secretory Diarrohea (Carcinoid syndrome, VIPoma) B. GH receptor antagonist
O → Oesophageal Varices – Pegvisomant
M → Malignancy [Insulinoma, Glucagonoma]
3. Gonadotropin Releasing Hormone [GnRH]
A → Acromegaly
Pulsatile Fashion Continuous Fashion (Non-pulsatile manner)
→ Any drug ending with “tide” is peptide. ↓ ↓
→ Any endogenous substance ending with “in” is a ↑ Gonadotropins ↓ Gonadotropins
peptide ↓ ↓
e.g; Somatostatin
Vasopressin ↑ Estrogen ↓ Estrogen
Oxytocin ↑ Progesterone ↓ Progesterone
→ Peptides cannot be given orally ↑ Testosterone ↓ Testosterone
Somatostatin → Short acting therefore not used Indications of GnRH
Octreotide → Long-acting somatostatin derivative
→ Given by SC route Pulsatile manner Continuous Fashion
1. Anovulatory infertility 1. Carcinoma prostate
2. Prolactin Inhibiting Hormone [PIH] =
2. Hypogonadotropic hypogonadism 2. Endometriosis
Dopamine [DA]
3. Delayed Puberty 3. Precocious Puberty
→ DA acts through D2 Receptors
→ Dopamine D2 Agonists decrease prolactin GnRH AgonistsQ
Examples 1. Leuprolide
Bromocriptine 2. Nafarelin (nasal route)
Cabergoline [Long acting] 3. Goserelin
4. Busurelin
5. Histarelin
→ Not effective orally (Mostly given by subcutaneous
route)
→ Flare up Reaction: When these are given in continuous
 41
Pharmacology
manner, for initial few days, there is aggravation of Vasopressin Receptor Agonists
disease
– V1 agonist is terlipressin
GnRH AntagonistsQ
• DOC for esophageal varicesQ
1. Cetrorelix
– V2 agonist is desmopressin
2. Ganirelix
• DOC for neurogenic (central) diabetes
3. Abarelix insipidus (Given by nasal route)Q
4. Degarelix
Vasopressin Receptor Antagonists
→ No Flare up reaction
– VAPTANS: VAsoPressin ANTagonistsQ
→ But they do not ↑ sex hormones (Used only to ↓ sex
hormones) – Examples
→ Not effective orally Conivaptan - Given via Intravenous route
Tolvaptan - Given via Oral route
ELAGOLIX
– Used for SIADH
→ Recently approved oral GnRH antagonist
→ Approved for pain due to Endometriosis THYROID
Hypothyroidism
POSTERIOR PITUITARY – DOC is L-thyroxine (T4)
→ Secretes two main hormones
– Started at 25 mcg daily
• Oxytocin
– Gradually the dose is increased
• Vasopressin

Oxytocin Hyperthyroidism
– Main function is to contract the uterus 1. Thyroid Peroxidase Inhibitors (Thioamides)
• DOC for augmentation of labour Carbimazole (Prodrug)
Propyl Thio Uracil (PTU)
• DOC for postpartum hemorrhage Methimazole (Active)

– Other function is ejection of milk → Crosses placenta easily → Less crossing of Placenta

• DOC for Breast engorgement → DOC for all patients

except in 1st trimester → DOC in 1st trimesterQ
of pregnancy
Vasopressin → Can cause choanal
– Also known as anti diuretic hormone (ADH) atresia and aplasia cutis → Lesser chance
in developing fetusQ
Vasopressin Receptors
2. Secretion Inhibitors
• Nal
V1 Receptor V2 Receptor
– Present on BV – Present on kidney • Kl
– Cause vasoconstriction – ↓ Urine. • Lugol’s Iodine
→ Fastest acting anti-thyroid drugs.
→ Given preoperatively:
– To make the gland small, firm and less vascular
– To reduce the blood loss during surgery.
42
Cerebellum Quick Revision Notes

3. Radioactive iodine or I131 • Anterior thigh

→ C/I in pregnancy Q
• Lateral thigh
→ Cause irreversible hypothyroidism • Arm
→ Physical t ½ is 8 days 2. Intravenous route:
• Only regular insulin can be given
ENDOCRINE PANCREAS • So, insulin of choice in diabetic Ketoacidosis
→ Regular insulin
Secretes Action Uses
α cells Glucagon ↑ Blood Sugar Hypoglycemia 3. Inhalational route:

β cells Insulin ↓ Blood Sugar Diabetes mellitus Afreeza → Short acting insulin → So, should be
Amylin given before every meal

δ cells Somatostatin ↓ Insulin Islet cell tumors

↓ Glucagon INSULIN ANALOGUES
Rapid acting Ultra-Long Acting
GLUCAGON • LISPRO • GLARGINE
Uses • ASPART • DETEMIR
• GLULISINE • DEGLUDEC (Longest Acting)Q
1. Hypoglycemia 2. Beta- Blocker Poisoning
– Glucagon is DOCQ
- These are peakless insulins
→ Acts by Glycogenolysis
– Acts by stimulating - These have low risk of hypoglycemia
→ Not useful in hypoglycemia
glucagon receptors on
caused by Side Effects
heart
• Starvation
1. Hypoglycemia
• Alcohol induced hypoglycemia
2. HypokalemiaQ

INSULIN
ORAL ANTI DIABETICS DRUGS
Indications
1. Insulin Secretagogues (Act by ↑ Insulin secretion)Q
1. All patients of type 1 DM
– These drugs secrete insulin and thus can cause
2. Uncontrolled patients of type 2 DM
hypoglycemia
3. Diabetes in pregnancy
Sulfonylureas Meglitinides
4. Diabetic Ketoacidosis
1st Generation Nateglinide
Routes of Administration Repaglinide
Chlorpropamide
1. Sub - cutaneous route:
Tolbutamide
– MC route (because self-administration is 2nd Generation
possible with this route)
Glipizide
– All insulin preparations can be given by Gliclazide
subcutaneous route. Glibenclamide
– Site of administration
Drugs ending with “IDE” can cause - hypoglycemiaQ
• Entire abdomen except area around umbilicus
(thickness of skin is not uniform, so insulin
absorption is affected)
 43
Pharmacology
2. Drugs Acting by Other Mechanisms C. Acarbose
→ Act by inhibiting the intestinal absorption of
A. Metformin carbohydrates (blood sugar decreases)
Adverse effects → Does not cause hypoglycemia
1. Megaloblastic Anemia → Flatulence → MC side effect
2. Lactic acidosis → C/I in lnflammatory bowel diseaseQ
Risk of lactic acidosis further ↑, if there isQ • Ulcerative colitis

– Liver disease (Gluconeogenesis cannot occur) • Crohn’s disease

– Renal disease (Lactic acid produced cannot be

NEW ANTIDIABETIC DRUGS
excreted)
1. Incretin – Mimetics
– Any condition predisposing to hypoxia (e.g.;
Shock, COPD) → Incretins are normal physiological substances
which are released in GIT after food intake that
Thus, metformin is C/I in these patients. stimulate the release of insulin.
→ Most important endogenous incretins are GLP
Indications (Glucagon like peptide) and GIP (Glucose
→ Metformin is DOC for Type 2 DM because: stimulated insulinotropic polypeptide)

– No risk of hypoglycemia → Functions of Incretins:

– Max. reduction in HbA1cQ – Increase insulin release
– Can cause weight loss or weight neutral (No – Decrease gastric motility
weight gain) → GLP is metabolized by DPP-4 and becomes inactive

B. Glitazones
E.g. Troglitazone
Rosiglitazone
Pioglitazone

Mechanism
Act by stimulating PPAR-ꝩ → Reversal of Insulin Resistance
Adverse Effects A. GLP analogues:
→ Given subcutaneously (Cannot be given orally since
1. Hepatotoxic
these are peptides)
→ Max. hepatoxicity → Troglitazone [withdrawn]Q
GLP-1 analogues : Used for type 2 DMQ
→ Rosiglitazone and Pioglitazone require LFT
– Exenatide
monitoringQ
– Liraglutide
2. Na+ and water Retention → Avoid in CHF and HTNQ
3. Predispose to osteoporotic fractures. GLP-2 analog : Used for short bowel syndromeQ

4. ↑ Risk of Ml by rosiglitazone – Teduglutide

5. ↑ Risk of urinary bladder carcinoma by PioglitazoneQ Side effects

– Acute pancreatitis (Major side effect)
– Increased risk of Medullary carcinoma of
Thyroid
44
Cerebellum Quick Revision Notes
B. DPP - 4 inhibitors: 4. BromocriptineQ
a. Sitagliptin → Decreases insulin resistance and it has been
b. Vildagliptin recently approved for type 2 diabetes treatment.
c. Alogliptin → Given in small dose and taken at early morning
on awakening.
d. Linagliptin

→ Gliptins are oral anti - diabetic drugs. ADRENAL

– Pancreatitis is the major adverse effect Adrenal Medulla Adrenal Cortex
– Gliptins are contraindicated in renal failure → Secretes → Secretes
except Linagliptin which is safe in renal failure – Adrenaline – Glucocorticoids
2. SGLT-2 Inhibitors: – Nor-Adrenaline – Mineralocorticoids
→ Glucose is freely filtered by glomerulus but the – Dopamine
clearance of glucose in urine is negligible.
Mineralocorticoids
→ Because the reabsorption takes place in proximal
Aldosterone → Major endogenous Mineralocorticoid
tubule by sodium glucose transporter (SGLT-2)
Actions
– Retain Na+ and water
– Remove K+ and H+
Glucocorticoids
Hydrocortisone → Major endogenous Glucocorticoid

CLASSIFICATION OF DRUGS
Glucocorticoids Mineralocorticoids
Short Acting (<12 hours) Aldosterone
Cortisone Fludrocortisone
→ SGLT-2 inhibitors stop the reabsorption of glucose Hydrocortisone DOCA
in PT resulting in glucosuria.
Intermediate Acting (12-36 hours)
Drugs areQ Prednisone
– Canagliflozin Prednisolone
– Dapagliflozin Triamcinolone

– Empagliflozin Long Acting (> 36 hours)

– Ertugliflozin Dexamethasone
Betamethasone
– Most common side effect of SGLT-2 Inhibitors
Paramethasone
is Urinary Tract infections
– SLGT-2 inhibitors provide cardiovascular benefits.
Special PointsQ
These are approved for treatment of CHF.
Property Drug
3. Amylin Analogs:
Maximum G activity Dexamethasone
→ Amylin is secreted form b - cells of pancreas. Maximum M activity Aldosterone
→ Function of amylin is to ↓ blood sugar. G with max M activity Hydrocortisone

→ Pramlintide is an amylin analogue M with max G activity Fludrocortisone

Triamcinolone
→ It is approved for both type 1 and 2 diabetes.
Selective G Dexamethasone
Betamethasone
 45
Pharmacology

Selective M DOCA Adverse effects

Note: G means glucocorticoid (anti-inflammatory) Major adverse effect is Cushing syndrome
M means mineralocroticoid (Na+ and H2O retaining)

Uses of Corticosteroids
Antenatal Replacement Other Uses
Dexa / Acute Adrenal Inflammation
Betamethasone insufficiency / Auto immune
for fetal Addisonian crisis diseases
lung maturity [by IV] Transplantation
(Glucocorticoids Anticancer therapy
increase Chronic Adrenal Asthma
surfactant lnsufficiency /
production) Addison’s disease
[by oral]

Ante Natal Steroids Total dose Total duration

Betamethasone → IM 12 mg
24 mg 48 hrs.
every 24 hrs. x 2 DosesQ
Dexamethasone → IM 6 mg OSTEOPOROSIS
24 mg 48 hrs
every 12 hrs. x 4 Doses
Drugs used in Osteoporosis
Hypothalamo-Pitutary-Adrenal Axis [HPA Axis]

Inhibit Dual action

Nutritional osteoclast Stimulate – Strontium
factors – Calcitonin osteoblast – Romosozumab
– Calcium – Estrogens – PTH 1-34
HPA Axis Suppression – Vitamin D – SERMs
– Denosumab
→ Occurs when corticosteroids are given continuously – Cinacalcet
for > 2wks
Preventive Measures Nutritional Factors
1. Stop unnecessary use of steroids – Calcium is given at a dose of 1200 mg/day (It
includes dietary calcium)
2. If indicated, prescribe them for minimum period
– Vitamin D should be given as 800 IU per day
preferably < 2wks
3. If indicated for long periods, prescribe them on Drugs Inhibiting Osteoclast
alternate day 1. Calcitonin: Given Intranasally
– Long-acting steroids (dexa, beta and 2. BisphosphonatesQ
paramethasone) are avoided
Alendronate
4. If indicated daily and for longer periods Risedronate
– Don’t Stop Abruptly Zoledronate

– Tapering should be done – Inhibit osteoclasts

– DOC for Osteoporosis [Osteoporosis due to any
reason]
46
Cerebellum Quick Revision Notes
– These are indicated for a period of maximum 10 DRUGS STIMULATING OSTEOBLASTS
years
1. Teriparatide
– Highly toxic to esophagus
– Parathyroid hormone contains 84 amino acids
Prevention of Oesophagitis Q (i.e., PTH1-84).
– Take empty stomach – Full molecule stimulates osteoclast and induces
– Take with full glass of water osteoporosis by resorption of bone.
– Remain upright for 30 min
– Teriparatide is a fraction of parathyroid (PTH
3. Estrogen and SERM 1-34) that stimulates Osteoblast and is used for
Decreased estrogen is responsible for post- osteoporosis treatment.Q
menopausal osteoporosis – Route of administration - Not effective orally
(given subcutaneously)
Actions of Estrogen
– PTH 1-34 is recommended for maximum 2 years.
Bone → Prevent resorption
– Treatment with PTH should be followed by
Blood → ↑ HDL/LDL Ratio 1-34
bisphosphonates.
Breast → ↑ Risk of Carcinoma
Endometrium → ↑ Risk of Carcinoma
Liver → ↑ Clotting Factors → Thromboembolism
DRUGS WITH DUAL ACTIONQ
→ Not preferred for Rx of PM Osteoporosis
– These have dual activity of stimulating
RaloxifeneQ osteoblast and inhibiting osteoclast
– It is selective estrogen receptor modulator – Strontium ranelate and romosozumab act by
dual mechanism
– It has agonist action on ER in bone, blood and
liver whereas antagonistic action on breast and – Romosozumab is a monoclonal antibody against
endometrium sclerostin
– Used in post menopausal osteoporosis ANDROGENS
– Additional Benefits – 5 a reductase converts testosterone into
• ↑ HDL Dihydrotestosterone (DHT) which works on
androgen receptors. Testosterone also can
• ↓ Breast and Endometrial carcinoma risk directly work on androgen receptors.
– Major S/E → Thromboembolism
4. Denosumab
– On the surface of osteoclast cells, RANK
receptors are present. When ligand binds to
RANK receptors, it stimulates the resorption of
bone.
– Denosumab is a monoclonal antibody against
RANK ligand. It inhibits the osteoclastic activity
and resorption of bone.Q

– In treatment of prostatic cancer androgen

receptor blockers are commonly used.
– In treatment of BPH and androgenital alopecia
(Male pattern baldness): 5 α-reductase inhibitors
like finasteride are used.
 47
Pharmacology
– Both the class of drugs can cause impotence as an 3. EMERGENCY CONTRACEPTIVES
adverse effect
A. Combined Oral Contraceptives
B. Progesterone Only Pills [LNG]
ORAL CONTRACEPTIVES C. Mifepristone
Above 3 drugs should be used with in 72 hrs. of
unprotected intercourse.
D. Ulipristal
→ Can be used within 120 hours of unprotected
intercourse

NON CONTRACEPTIVE BENEFITS

OF OCPs
Other → ↓ Ovarian cyst [DOC for PCOD]
B → ↓ Benign Breast Disease
1. COMBINED ORAL CONTRACEPTIVE PILLS
E → ↓ Endometriosis
→ Drugs
N → ↓ Neoplasia [Endometrial and ovarian cancers]
• Estrogen - Ethinyl Estradiol
E → ↓ Ectopic pregnancy
• Progesterone - Levonorgestrel
F → ↓ Fibroid
→ Dosage
I → ↓ Iron deficiency Anemia
• 1 tablet daily for 21 days from 1st day of
T → ↓ Premenstrual Tension Syndrome
menstrual cycle
S → ↓ Skeletal Disease [Osteoporosis]
• No tablet for next 7 days
• To ↑ compliance: 28 tablets strip with 1st
21 tablets contains drug and next 7 tablets OCPs
contains iron

→ Missed Tablets ↑ Risk of ↓ Risk of

– Cervical Ca – Endometrial Ca
If one tablet is missed Take 2 tablet on next day
– Breast Ca – Ovarian Ca
• Discard remaining tablets
• Practice other method of
If 2 or more tablets
contraception with it. POLYCYSTIC OVARIAN DISEASE
missed
• Start a fresh from next (PCOD)
cycle
– OCPs are DOC for regulating the menstrual
2. POP / MINIPILLS cycle in PCOD
– Metformin is used to reverse insulin resistance
– Used where Combined OCPs cannot be used
– Ovulation inducers are used to induce ovulationQ
– Contains LNG
• Aromatase inhibitors e.g. letrozole is DOC
– OCP of choice in lactationQ
• Clomiphene citrate can also be used.
48
Cerebellum Quick Revision Notes

Previous Years Questions Q6. A 28 year old female with Graves’ disease was taking
medication for hyperthyroidism during pregnancy.
Q1. A patient was operated for prostate carcinoma and She delivered a child with congenital anomaly ‘aplasia
during surgery local metastasis was noted. Which of the cutis congenita’. Most likely drug implicated for this
following drug this patient should receive? teratogenic effect is?
A. Leuprolide B. Desmopressin A. Carbimazole B. Levo-thyroxine
C. Octreotide D. Tamsulosin C. Methylthiouracil D. Liothyronine

Q2. Tolvaptan is used for: Q7. Drug of choice for hyperthyroidism in third
trimester of pregnancy is
A. SIADH
B. Central Diabetes Insipidus A. Carbimazole B. Propylthyouracil
C. Von Willebrand Disease C. Sodium iodide D. Radioactive iodine
D. Catecholamine resistant Shock
Q 8. A 30 year old female presented with weight gain
and cold intolerance. On investigations Value of T3 is
Q3. A patient presents with pituitary tumor that
70 ng/dl (reference value 100-200 ng/dl),T4 is 3 mcg/
overproduces growth hormone. surgical removal of the
dl (reference value 5-12 mcg/dl) and TSH is 20 mIU/L
tumor was incomplete. What is the first line treatment
(reference value 0.5-5 mIU/L). Which of the following
of this patient?
statement is correct regarding the management of this
A. Leuprolide B. Octreotide patient?
C. Nafarelin D. Goserelin A. Measure T3, T4 and TSH after one month

Q4. A 40 year old male presents with protrusion of chin, B. Start L-thyroxine (T4) treatment 100 mcg once
daily
excessive sweating, impaired glucose tolerance and
enlargement of hands and feet? Which of the following C. Start L-thyroxine (T4) treatment 25 mcg daily and
drugs is a growth hormone receptor antagonist used to gradually increase
treat this condition? D. Start daily L-thyroxine (T4) 100 mcg with Liothy-
ronine (T3) 5 mcg
A. Pegvisomant B. Octreotide
C. Cabergoline D. Olcegepant
Q 9. What is the Drug of choice for Hyperthyroidism in
Q5. A female presented with galactorrhea. Her urine first trimester of Pregnancy?
pregnancy test was negative. MRI of head revealed A. Lugol’s iodine B. Methimazole
a large pituitary tumor. Patient refused to undergo
C. Propylthiouracil D. Carbimazole
surgery for the tumor. Which of the following is the
best drug for the treatment of this patient? Q 10. Which of the following drug is given pre-operatively
A. Octreotide B. Bromocriptine to decrease the risk of intraoperative bleeding in a
hyperthyroid patient planned for thyroidectomy?
C. Promethazine D. Clozapine
A. Potassium iodide B. Propranolol
C. Propylthiouracil D. Methimazole

Answers
1. - A 3. - B 5. - B 7. - A 9. - C
2. - A 4. - A 6. - A 8. - C 10. - A
 49
Pharmacology
Q 11. A 70 year old patient has diabetes mellitus and Q 16. Which of the following drug is given to mother
hypertension. He presents with late stage chronic delivering premature baby for fetal lung maturation?
kidney disease. Which of the following anti-diabetic
A. Aspirin
drugs require least dose modification in renal disease?
B. Dexamethasone
A. Sitagliptin B. Vildagliptin
C. Magnesium sulfate
C. Linagliptin D. Saxagliptin
D. Depot medroxy progesterone acetate
Q 12. A 50 year old patient of type 2 diabetes mellitus
was controlled on oral hypoglycemic drugs. This patient Q 17. A patient presented with the following features
presented to hospital with profuse sweating and after chronic intake of a drug for several years. Which
dizziness. There was presence of hypoglycemia. Which is the likely drug person has consumed?
among the following drugs can result in hypoglycemia in A. Paracetamol B. Prednisolone
this patient?
C. Phenytoin D. Metformin
A. Metformin B. Voglibose
C. Vildagliptin D. Glipizide

Q 13. Which of the following anti-diabetic drugs is

associated with increased risk of fractures in a female
with osteoporosis?
A. Canagliflozin B. Rosiglitazone
C. Voglibose D. Rapaglinide

Q 14. Mechanism of action of exenatide in diabetes

mellitus is
A. It is analogue of GLP released from gut and in-
crease glucose dependent insulin secretion

B. It is DPP-4 inhibitor and result in decreased

breadkdown of GLP

C. It inhibits SGLT-2 and cause glucosuria

D. It is amylin analogue and decrease glucagon Q 18. What is the prenatal dose of dexamethasone
given for lung maturation in premature infants ?
Q 15. To minimize the risk of HPA axis suppression, A. 6 mg 2 doses 12 hours apart
what is the correct method of administration of
B. 12 mg 2 doses 24 hours apart
prednisolone?
C. 6 mg 4 doses 12 hours apart
A. Give at night just before bedtime
D. 6 mg 4 doses 24 hours apart
B. Divide in three doses and give small doses 8 hourly
C. Give on alternate day
D. Replace with betamethasone

Answers
11. - C 13. - B 15. - C 17. - B
12. - D 14. - A 16. - B 18. - C
50
Cerebellum Quick Revision Notes
Q 19. Which of the following is not used in treatment of Q 21. A 22 year old female presents 8 hours after
polycystic ovarian disease? sexual assault. It is the 13th day of her menstrual cycle.
Which emergency contraceptive should be prescribed
A. Letrozole
to her?
B. Clomiphene citrate
A. Levonorgestrel 1.5 g single tablet
C. Ulipristal
B. Injection DMPA
D. Combined oral contraceptives
C. OCP from day 1 of next cycle
Q 20. Combined oral contraceptive pills act by all of the D. Misoprostol
following mechanisms except?
Q 22. Which of the following is not used as emergency
A. Inhibit implantation by bringing change in the uterus
contraceptive?
B. Inhibit ovulation
A. Danazol
C. Makes cervical mucus thick and hostile
B. Levonorgestrel
D. Increase gonadotropin secretion
C. Mifepristone
D. IUCD

Answers
19. - C 21. - A
20. - D 22. - A
 Physiology Revision 7 07 53

PHYSIOLOGY REVISION 7 ----- Active space -----

Endocrine Physiology 00:00:15

Forms of cell signalling:

Nearby
cell Autocrine signalling Gap Junctions

Paracrine signalling Endocrine signalling

far away cell
Classification of Hormones :
Class 1 : Amino acid derivatives.
Ex : Tyrosine Epinephrine, Norepinephrine, Dopamine.
Class 2 : Large protein hormones.
Ex : Insulin (51 amino acids), Parathyroid Hormone (84 amino acids).
Class 3 : Cholesterol derivatives.
Ex : Aldosterone, cortisol, testosterone, estrogen, progesterone.
Class 4 : Vitamins.
Ex : Vitamins A and D.

Hypothalamic and Pituitary Hormones 00:03:21

Most of the anterior pituitary hormones will have negative feedback except LH
surge (Increase in estrogen causes increase in LH levels).
Hypothalamic Releasing factors :
Hypothalamic hormones Anterior pituitary hormones
Thyrotropin-releasing hormone (TRH) Thyroid stimulating Hormone (TSH)
Adreno corticotrophin Releasing
Corticotropin-releasing hormone (CRH)
Hormone (ACTH)
Gonadotropin-releasing hormone Follicle Stimulating Hormone (FSH),
(GnRH) Luteinizing Hormone (LH)
Growth hormone-releasing hormone
Growth Hormone
(GHRH)
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 54 07 Physiology

----- Active space -----

Hypothalamic Inhibitory Hormones :
• Prolactin Release Inhibiting Hormone Dopamine.
• Growth Hormone Inhibiting Hormone Somatostatin.

Anterior and Posterior Pituitary Hormones :

Cell type Hormone

Anterior pituitary hormones
Acidophilic Somatotrope Growth Hormone
cells Lactotrope Prolactin
Gonadotrope FSH, LH
Basophilic
Thyrotrope TSH
cells
Corticotrope ACTH
Posterior pituitary hormones:
Stores and releases Oxytocin and Vasopressin

Growth Hormone 00:08:01

Regulation of Growth Hormone secretion :

Hypothalamus -

GHRH Somatostatin
+ -
+ Somatotrophs in anterior -
Ghrelin
pituitary
Growth Hormone
Liver

Insulin Like Growth factor -1

(IGF -1) Or Somatomedin-C

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 Physiology Revision 7 07 55

Factors influencing growth hormone secretion : ----- Active space -----

Factors that increase growth Factors that inhibit growth

hormone secretion hormone secretion
• Low blood glucose (GH is a • Somatostatin
diabetogenic hormone) • Increase in blood glucose levels
• Exercise (Eg : glucose infusion)
• Fasting • REM sleep
• Stress
• Starvation
• Deep sleep (NREM stage 3 &4)

Actions of growth hormone :

Direct actions :

Direct actions of growth hormone (Anti insulin like)

Decreased insulin Protein Sodium Lipolysis

sensitivity synthesis retention

Indirect Actions:

Indirect actions of growth hormone

IGF-1 (Insulin like activity)

Anti lipolytic Protein Epiphyseal growth

synthesis

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----- Active space -----

Prolactin 00:13:32

Regulation of prolactin secretion :

Regulation of prolactin secretion

Hypothalamus

Thyrotrophin releasing Prolactin inhibiting factor

hormone (TRH) (Dopamine)
+ -
Lactotrophs in anterior pituitary
+ -
Vasoactive intestinal Glucocorticoids
peptide (VIP) Thyroid hormones
Prolactin

Factors influencing prolactin secretion :

Factors increasing prolactin Factors inhibiting prolactin
secretion secretion
• Marked increase during • Somatostatin
pregnancy and lactation • Dopamine agonists
• Sexual intercourse (Like Bromocriptine)
• Dopamine blockers

Thyroid Hormones 00:15:48

Thyroid hormone synthesis :

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----- Active space -----

Made up of tyrosine and iodine from diet Thyroid hormone binding proteins :
• Thyroid binding globulin
• Albumin
• Prealbumin/ transthyretin : Binds to thyroid hormone and Vitamin A

Difference between T4 and T3 :

T3 (Physiological actions) T4 (pharmacological drug form)

It is more potent
Half-life : 1 day (less)
Plasma protein binding is less
Action is fast
Less in colloid (7%)
It is less potent
Half-life : 7 days (more)
It bind more tightly to plasma proteins
Action is slow and sustained
More in colloid (35%)

Effects of thyroid hormone :

Target tissue Effect Mechanism
Throughout Calorigenic Stimulates O2 consumption.
the body in basal metabolic rate.
Heart Chronotropic and Increased number of
inotropic ß-adrenergic receptor
(Norepinephrine mediated).
Adipose tissue Catabolic Stimulates lipolysis.
Muscle Catabolic proteolysis.
Bone Developmental Promote normal growth and
skeletal development.
CNS Developmental Promotes myelination.
Cholesterol Catabolic Cholesterol levels.

Endocrine Pancreas 00:25:10

Cell type Secretion

A cells (or) Alpha cells Glucagon
B cells (or) Beta cells Insulin, Amylin, C peptide
(60 – 75%), maximum
Lie in center of islets
D cells (or) Delta cells Somatostatin
F cells Pancreatic polypeptide

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 58 07 Physiology

----- Active space ----- Insulin:

Major anabolic hormone (Hormone of insurance).
Produced by Cells in the islets of Langerhans (Abundant in tail of pancreas).

Steps in release of insulin in islet of Langerhans :

Beta cells of pancreas
Apical end Step-3
Basolateral end Voltage sensitive Ca2+ channel
K+ accumulation
Step-2 VSCC Ca2+
K+ Ca2+
ATP sensitive K+ channel
K+ channel closed
GLUT-2 Glucose RMP =-90 mV
SNARE
Increased Step-1 protein
blood Increases ATP
I Step-4
glucose I I Exocytosis
of insulin

Factors that influence insulin secretion :

Factors that increase insulin secretion Factors that inhibit insulin secretion
• Glucose : Most potent factor. • Somatostatin
• Aminoacids Ex : Arginine, leucine
• Sympathetic discharge : • Sympathetic discharge :
ß-Adrenergic receptor mediated -Adrenergic receptor
• Parasympathetic : mediated
Vagal stimulation and acetylcholine • Streptozocin.
• Incretin hormones :
GI hormones like glucagon-like
peptide-1 (GLP1) and gastric inhibitory
peptide (GIP).

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 Physiology Revision 7 07 59

Mechanism of action of insulin : ----- Active space -----

Insulin receptor

Cell membrane

Tyrosine kinase

Insulin receptor substrates (IRS)

PI3 Kinase MAP kinase

Decreases blood glucose Mediates growth promoting

levels via GLUT-4 mediated and anabolic functions
facilitated diffusion

Influence of insulin in metabolic pathways :

Pathways stimulated by Insulin Pathways inhibited by Insulin

Glycolysis Glycogenolysis
Glycogenesis Gluconeogenesis
Lipogenesis Lipolysis

Hyperglycemic hormones :
Hormones antagonizing action of insulin hyperglycemia.
a.k.a counter regulatory hormones :
• Cortisol
• Growth hormone
• Glucagon
• Epinephrine
• Thyroid hormone

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 60 07 Physiology

----- Active space ----- Adrenal Gland 00:35:19

Zona glomerulosa :
Secrete Aldosterone
Zona fasciculata :
Secrete cortisol

Zona reticularis :
Secrete sex steroids
Adrenal medulla
Secrete
Catecholamines

Aldosterone
Actions : Collecting duct
Aldosterone acts on principal cell of Blood
Distal convoluted tubule vessel
I-cell
• Reabsorption of sodium : Through
Epithelial Na channels (ENac) in luminal H+-K+
Exchanger
surface Aldost H+
Na
• Reabsorption of water MR
Urine
Al
• Excretion of potassium ions in urine : Complex
HCo3-
Through Renal Outer Medullary K+
HCo3--Cl-
channels (ROMK channel). Exchanger

• Excretion of H+ ions in urine

Stimulus for aldosterone release :

• Increase in K+ concentration.
• Renin Angiotensin Aldosterone System (RAAS) : Angiotensin II.
• ENac channel blocker : Amiloride, Triamterene.

Note : Liddle’s syndrome : Hypernatremia, Hypertension, Hypokalemia

Occurs d/t Gain of funtion mutation of ENac channel.

Aldosterone escape :
Normally increase in aldosterone causes sodium reabsorption.
To prevent indefinite reabsorption of sodium, Atrial natriuretic peptide (ANP) is
secreted to promote sodium excretion
Hence the sodium excreted despite the presence of aldosterone.
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 Physiology Revision 7 07 61

Cortisol : ----- Active space -----

Effect Mechanism
On carbohydrate
“Hyperglycemic hormone” gluconeogenesis
metabolism
• Catabolic to proteins present in the muscle
On protein
• Anabolic in liver : synthesis of plasma proteins
metabolism
from liver
On fat metabolism Lipolytic
On immune system Universal anti-inflammatory agent
• Cortisol the blood levels of : Eosinophils, Lympho-
cytes, Basophils
On blood cells
• Cortisol the blood levels of : Neutrophils,Platelets,
RBCs
• Alters mood and behaviour
On nervous system
• appetite
On kidney • glomerular filtration rate and calcium excretion
On bone bone resorption by activity of osteoclasts
On connective Inhibits fibroblast proliferation and collagen formation
tissues (Delay wound healing)

Adrenal Sex steroids :

Adrenal sex steroids produced from zona reticularis are :
• Dehydroepiandrosterone/DHEA (Maximum).
• Dehydroepiandrosterone sulfate (DHEAS).
• Androstenedione.
• Testosterone (Only small amounts).
Role in : Axillary and pubic hair development, libido.

Calcium Homeostasis 00:47:41

Normal value of calcium : 8.7 - 10.2 mg/dL

Ionized calcium
Around 50% of total calcium
Also called as free calcium or
diffusible calcium
Physiologically active form
Protein bound calcium
Remaining 50% of total calcium
Also called as non diffusible calcium
Storage form bound to albumin and
globulin

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----- Active space ----- pH changes and calcium :

Acidosis Alkalosis

Increased H+ ions Decreased H+ ions

Bind to albumin Calcium binds to albumin

Increased free calcium Decreased free calcium

Hypercalcemia Hypocalcemia

Absorption of calcium :
• Calcium absorption occurs mainly in duodenum.
• Absorption of calcium is facilitated by gastric acid, protein rich diet.
• Absorption of calcium is inhibited by phytates and oxalates (Form complexes
with calcium).

Hormonal regulation of calcium levels :

PTH Vitamin D Calcitonin

Stimulus in S. Ca2+ in S. Ca2+ in S. PO43- in S. Ca2+
in PTH
Bone bone resorption Both bone Inhibits bone
mineralization and resorption
resorption
Intestine Indirectly acts by S. Ca2+ & S. PO43- -
vitamin D absorption
Kidney S. Ca2+ resorption S. Ca2+ & S. PO43- S. Ca2+
S. PO43-excretion resorption excretion
(phosphaturic)
Overall effect S. Ca2+ & S. PO43- S. Ca2+ & S. PO43- in S. Ca2+

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