E

N
D
O
C

/e
14 R
I
S,
AM

N
O
O
R

L
O
G
Y
 E 15.1 BASICS OF ENDOCRINOLOGY Some Conditions a/w hypo-/hyperglycemia
N Hypoglycemia Hyperglycemia
D Chemical Nature of Hormones •• Hypopituitarism •• Hyperpituitarism
O •• Adrenal insufficiency (Acromegaly)
C Chemical composition Example •• Hepatitis •• Hyperadrenalism, Cushing
R •• Peptide Hm Insulin, PTH, Renin, Ang II, ADH, ANP •• Hypothyroidism syndrome
•• Insulinoma
I
•• Amines T3, T4, Adr, NA, Dopa
N
•• Glycoproteins FSH, LH, TSH, hCG, Erythropoietin
O
Diurnal variation of Hormone secretion
L
O ƒƒ GH secretion: Maxm at night (onset of sleep).
Hormones with intracellular receptors ƒƒ Melatonin: Maxm at night (lower at day).
G
Y ƒƒ Cytoplasmic → Glucocorticoids, mineralocorticoids, ƒƒ ACTH and corticosteroid secretions: Maxm at early
androgens, progestins. morning (minm in night).
ƒƒ Nuclear → Estrogen, T3T4, Retinoic acid, Vit-D. ƒƒ The diurnal variation of melatonin is brought about by NA
(nor adrenaline).

/e
Second Messengers for Hormones In dark NA secretion is ↑ed → acts on b receptor → ↑
cAMP → ↑ N-acetyl transferase (enzyme involved
20 messengers Example
in melatonin synthesis from serotonin) activity. → ↑

14
•• cAMP CRH, FSH, LH, TSH, ACTH, PTH, hCG, melatonin 5- methoxy tryptamine.
Vasopressin, (V2 receptor), calcitonin,
somatostatin, Dopamine (D1, D2),
glucagon, Histamine, GABAB, AngII
•• cGMP ANP, NO, EDRF 15.2 PITUITARY HORMONES
S,
•• Enzyme linked R GH, Prolactin, insulin, EGF, PDGF, FGF
Anterior pituitary hm Posterior pituitary
•• Intrinsic ion channel GABAA, 5-HT3, Ach (nicotinic (adenohypophysis) (neurohypophysis) hm
cholinergic receptors)
Acidophil cells Basophil cells Oxytocin
AM

ADH (AVP or
Hormones in Stress (Fear Response) GH (from ACTH
Vasopressin)
somatotrope) (Corticotropes)
↑se secretion of ↓se secretion of Prolactin (from TSH (thyrotropes)
lactotrope) FSH, LH (from
•• Adrenal hormones •• Anabolic hormones gonadotropes
(Epinephrine, NE •• Insulin
O

cells)
Cortisol) •• Testosterone
•• Glucagon, •• FSH,LH ƒƒ ↑ GH and ↓ sometomedin levels are seen in Kwashiorkor.
•• ACTH,
R

•• Renin, Ang-II, Aldosterone ƒƒ Cong. abnormality of GH receptors → Laron dwarfism.

ƒƒ ↑↑ GH during adolscence (before epiphyseal fusion)
↑ Lipolysis
results in → Gigantism (giantism).
↑ Venoconstriction,
ƒƒ ↑↑ GH after epiphyseal fusion results in → Acromegaly
↑ peripheral resistance
(M/c cause of acromegaly is acidophil tumour of anterior
ƒƒ Stress induced hyperglycemia is mediated by → pituitary).
Epinephrine, cortisol, glucagon (by stimulation of ƒƒ Effect of pituitary destruction/compression by tumour:
gluconeogenesis). Results in trophic hormone failure in order of GH > FSH >
LH>TSH > ACTH (affected lastly).

582
HORMONES: SUMMARY
Gland Cells Hormones Chemical Site and action Excess manifestation Deficiency
nature manifestation
•• Pineal gland Pinealocytes Melatonin Biological clock
•• Ant. pituitary (Ad- Acidophil Somatotropes → GH Gp Before epiphyseal fusion → Gigantism, Dwarfism
enohypophysis) R After epiphyseal fusion → Acromegaly
Lacto/mammotropes → PP ↑ in number during Galactorrhoea, hypoestrogenism with -
Prolactin pregnancy & lactation anovulatory infertility
Basophil Corticotropes → PP Cushing's d/s
ACTH
O
Gonadotropes → PP Early growth of ovarian
Gn , FSH follicle
Gonadotropes → PP Final maturation of Delayed puberty,
Gn, LH ovarian follicle growth hypogonadism
AM
•• Intermediate lobe Basophil Orexins, MSH (stimulate
of Pituitary MSH melanocytes)
•• Post. Pituitary Oxytocin PP No ?Depression
•• (Neurohypophy- ADH (AVP or Vasopressin) SIADH Diabetes insipidus
sis)
•• Thyroid Follicular cells T3, T4 (Thyroxine) Amines Regulate Thyrotoxicosis (Grave's d/s) Hypothyroidism
S,
metabolism,dvpt of
thyroid. Bone, brain
growth, BMR, b
-adrenergic effects
14
Para-follicular Calcitonin Ca++ homeostasis
("C") cells
•• Parathyroid Principal/chief Parathormone PP Bone resorption, retains Loss of bone minerals, hypercalcemia hypoparathyroidism,
/e
cells Ca, excretes phosphates Tetany, carpopedal
spasm,stridor in chil-
dren
Contd...
I

L
E

Y
N
R
C
D
N

G
O
O
O

583
584
I

L
E

Y
N
R
C
D
N

G
O
O
O

Gland Cells Hormones Chemical Site and action Excess manifestation Deficiency
nature manifestation
•• Adrenal/ ZG (Glomeru- Mineralocorticoids Steroid Acts on DT in kidney, Na+ Conn's Addison's d/s
Suprarenal cortex losa) (Aldosterone) reabsorption, syndrome
R Controls Renin-
angiotensin
ZF Gluco-corticoids (Cortisol, Steroid CBH, protein, lipid Cushing's
(Fasciculata > corticosterone)
O metabolism syndrome
reticularis)
ZR (Reticularis) Adrenocorticoids, Steroid
androgens (mainly DHEA)
•• Adrenal/ Chromaffin cells Epinephrine (Adr) Catechola- ↑se HR, BP, RR; (Fight or
AM
Suprarenal mines flight response)
medulla
Norepinephrine (NE) Catechola- Peripheral
mines vasoconstriction
•• Pancreatic islets a -cells Glucagon ↑se sugar Hyperglucagonemia -
S,
(of Langerhans)
b -cells Insulin PP ↓se sugar Hypoglycemia DM
d -cells Somatostatin Inhibit secretion of a >
b cells
14
Other cells PP, VIP,
Secretin ©VDA
/e
ƒƒ Pituitary adenoma: ƒƒ 2-cell, 2-gonadotropin hypothesis: LH induces androgen E
°° Two types: synthesis by theca interna cells, whereas both FSH and N
LH stimulate aromatase activity by granulosa cells. D
The joint action of these two types of cell and pituitary
O
hormones forms the basis of a 2-cell, 2-gonadotropin
Microadenoma Macroadenoma C
°° Size <1cm °° Size >1cm hypothesis for biosynthesis of estrogen.
R
°° Do not invade °° Invade parasellar ƒƒ Best test for ovarian reserve → AMH.
parasellar region region & beyond I
ƒƒ Indicators of poor ovarian reserve are → Advancing age,
N
↑ FSH > ↓ Inhibin.
O
Somatomedins (IGF) ƒƒ Inhibin and follistatin supress FSH → Delay puberty
L
ƒƒ Polypeptide growth factors secreted by liver and other ƒƒ Activin A activates puberty → Early puberty.
O
tissues. ƒƒ Progesterone peaks at 21 days of cycle. It is responsible for
G
ƒƒ Somatomedin-C is also k/as IGF-I, mainly involved in secretions for nutrition of zygote.
Y
skeletal and cartilage growth. It mediates chondroitin ƒƒ Endometrial regeneration starts on day 5 of cycle.
sulfate deposition. ƒƒ High prolactin levels are a/w high FSH.
ƒƒ MSA or IGF-II is mainly involved in growth during fetal

/e
development.
ƒƒ Acromegaly is d/to ↑in GH. 15.3 THYROID HORMONES

14
Gonadal Hormones: LH and FSH THYROID HORMONES & TFT (THYROID
Role / Function LH FSH FUNCTION TESTS)
1. Οvarian follicle growth Final maturation Early growth ƒƒ ↑es HR to meet the to meet the ↑ed oxygen needs.
2. Aromatase activity - + nt ƒƒ T3 directly boosts energy metabolism in mitochondria.
S,
3. Role in formation + - ƒƒ Stimulates brown adipose tissue, a mitochondria-rich
of CL, progesterone tissue, to boost heat production in mammals without
secretion muscle activity.
AM

2. Aromatase activity - + nt ƒƒ Triggers rapid protein synthesis.

ƒƒ Estrogen partially blocks the efficiency of thyroid hm, so
2. Receptors present on Granulosa cells, Granulosa
women compensate by producing more thyroid hm than
theca interna in cells in
females females men.
Leydig cells in Sertoli cells in ƒƒ Transported in blood with prealbumin, albumin and
globulin.
O

males males
ƒƒ In thyroid follicles thyroxine is stored for 2-3 months.
R

Comparison of Actions of Dopamine Vs TRH

Dopamine TRH
Normally ↓ Prolactin, ↑ ↑ T3, T4, ↑ Prolactin,
GH No effect on GH
In Prolactinoma ↓ Prolactin No or little ↑ Prolactin
In Acromegaly ↓ GH ↑ GH

T3, T4, RT3

ƒƒ LH acts only on FSH primed granulosa cells. FSH ↑es
no. of receptors for LH to act upon. Aromatase catalyzes
conversion of androstenedione to estrone and testosterone
to estradiol.
ƒƒ T3 is more active, more potent and has maximum affinity
for albumin.
ƒƒ RT3 (Reverse T3) is is a biologically inactive form of
T3. Normally, when the liver converts T4 to T3, it also
produces a certain percentage of RT3. Serum RT3 (Reverse
T3) is useful for d/g of nonthyroidal illness syndrome.
585
 E ƒƒ T4 is inactive and more tightly bound to plasma protein TRH Stimulation Test
(T4 is major circulating thyroid Hm). TBG protein binds
N ƒƒ TRH stimulates the release of TSH, Prolactin, GH
maximum to T4.
D ƒƒ TRH induced GH stimulation may occur in acromegaly,
O MIT + T3 T4 T3 (active form) anorexia nervosa, uremia, PEM (conditions with ↑ Basal
C ƒƒ Half life of T3 → 1 day. GH level)
R ƒƒ Half life of T4 → 6 day. ƒƒ TRH stimulation is useful in supporting a d/g of
I ƒƒ Wolff–Chaikoff effect: During initial iodine exposure, hyperthyroidism, recurrent acromegaly, Gn secreting
N excess iodine is transported into the thyroid gland by tumours.
O the sodium–iodide symporter. This transport results in
L transient inhibition of TPO and a decrease in the synthesis
High-yield Points
O of thyroid hormone. 44 T4 and TSH levels are unaffected by gout.
G ƒƒ Serum TSH is single best for screening of hypothyroidism. 44 T3 ↓↓ occur during starvation.
Y ƒƒ Cord blood FT4 and TSH are used to screen hypothyroidism
in newborn.
THYROIDITIS
Interpretation of Thyroid Function Tests

/e
Type De Quervain's Riedel's Hashimoto's
T4 FT4 TSH Interpretation Also Granulomatous Painless Lymphadenoid
↓ ↓ ↑ Primary hypothyroidism k/as goitre

14
N N ↑ Transient compensated hypothyroidism Cause Precipitated by Compression Familial,
viral infection/ Anti-TPO/TBG/
↓ ↓ N Central hypothyroidism URI microsomal
↑ ↑ N Hyperthyroxinemia antibodies +
Thyroid Firm, tender, Stony hard, Sporadic goitre in
S,
↓ N N Low TBG
Gland enlarged painless goitre children
↑ ↑ ↑ T4 Resistance TFT Hyperthyroidism ↓ Ca++, Hypo- Hyper → hypo
thyroidism →N
AM

Radioactive Iodine Uptake (RAIU) Lab ↑ ESR, ↓ RAIU Mediastinal/ Follicular and
ƒƒ Thyroid uptake is seen in → Thyroid gland, salivary gland, RP fibrosis Hurthle cell
hyperplasia,
mammary gland, gastric mucosa, placenta.
Plasma cell/
ƒƒ I131 uptake (RAIU) is ↑ in 'hot' nodule (d/to uptake by lympho infiltration
functional tissue) and 0 (no uptake) in 'cold' nodules.
Rx NSAIDs Tamoxifen/ Thyroxine
O

ƒƒ RAIU is ↓ in steroids,
°° De Quervain's thyroiditis, subacute thyroiditis Partial
°° Silent/painless thyroiditis (Reidel's) removal
R

°° Factitious hyperthyroidism. ƒƒ Most common cause of thyroiditis is hashimotos thyroiditis.

°° Iodine overload ƒƒ M/c cause of hypothyroidism with goitre in children -
ƒƒ RAIU is ↑ in overactive gland (E.g. Graves disease, toxic Autoimmune thyroiditis (Chronic lymphocytic thyroiditis).
multinodular goitre, single thyroid nodule)

Anti-Thyroid antibodies
ƒƒ Anti- thyroid antibodies are useful for d/g of auto-immune
thyroiditis.
ƒƒ Anti-microsomal Peroxidase antibodies (TPO) have
highest titre in Hashimoto's thyroiditis and moderately
elevated in Graves' disease.
ƒƒ LATS antibodies (long-acting thyroid stimulator) are
also known as thyroid-stimulating antibody (TSAb),
TSI (Thyroid stimulating immunoglobulins) are directed
against a TSH receptor on the thyroid gland.
586
°° TSI are immune marker for Graves' disease.
°° TSI are also found in multinodular goiters. Fig.: Multinodular goiter
HYPERTHYROIDISM ƒƒ CF: E
°° Normal birth weight and length, N
ƒƒ Jod- Basedow phenomena is excessive thyroid hormone
°° Prolongation of physiological jaundice, D
synthesis d/to ↑ iodine exposure.
°° Coarse facies, low hair line O
ƒƒ Wolff-Chaikoff effect is suppressive action of excessive
°° Feeding difficulties, constipation, C
iodies, which transiently inhibits thyroid I- organification.
°° There is stunting of growth, delayed bone age, wide R
ƒƒ Pemberton's sign is compression effect of large retrosternal open fontanels, hypotonia.
goitre. I
°° Epiphyseal dysgenesis is pathognomonic. Epiphyseal
ƒƒ Pendred syndrome is sensori-neural deafness + partial N
centres that are normally present at birth like upper end
organification of thyroid. O
of tibia, lower end femur in the knee joint and talus,
ƒƒ CVS manifestations: L
calcaneum, cuboid in ankle joint. These centres may be
°° ↑ in cardiac output O
absent in X ray in congenital hypothyroidism.
-- Palpitations, systolic hypertension G
°° Disproportionate dwarfism (infantile proportions are Y
-- Sinus tachycardia (m/c manifestations) retained).
-- Hyperdynamic precordium
°° Some children with juvenile hypothyroidism exhibit
-- Mid systolic murmurs (systolic ejection click) unexplained precocious puberty.
°° Means -Lerman scratch: systolic scratchy sound.

/e
ƒƒ Diagnosis:
°° Pretibial myxoedema may be seen. °° Screening test for congenital hypothyroidism is Serum
ƒƒ T/t: TSH.

14
°° PTU, carbimazole, methimazole (active metabolite of °° Neonatal screening tests are: Cord blood TSH, FT4, T3
carbimazole) : All inhibit TPO estimation. There is ↑ TSH (most specific), ↓ T4 and
°° Propranolol T3 may be normal.
°° Radio iodine (I131) is useful Best time for test is : 2days - 6 days. In first 24 - 48 hrs,
°°
High-yield Points there is TSH surge. False +ve results are more with cord
S,
blood.
44 DOC in thyrotoxic crisis is large doses of propylthiouracil as it
blocks T4 to T3 conversion.
AM
O
R

Fig.: Thyrotoxicosis with myopathy

Fig.: Hypothyroidism pre treatment, Look at the coarse facies

HYPOTHYROIDISM
Congenital Hypothyroidism
ƒƒ Congenital hypothyroidism is M/c preventable cause of
mental retardation.
ƒƒ M/c neonatal disorder to be screened in neonatal period.
ƒƒ M/c cause of congenital hypothyroidism is thyroid
dysgenesis (dyshormonogenesis).
ƒƒ M/c cause of hypothyroidism with goitre in children -
Autoimmune thyroiditis (Chronic lymphocytic thyroiditis).
Acquired Hypothyroidism (Myxoedema)
ƒƒ Caused by destruction of thyroid d/to autoimmune
lymphocytic infiltration, irradiation, following surgery.
ƒƒ Presents with stunting of growth, cold intolerance, excess
sleepiness, delayed bone age, subnormal intelligence
ƒƒ Hypothyroidism in a pt with IHD is treated by → low dose
of levothyroxine.
ƒƒ Hung up reflex: DTR in which after a stimulus is given
and reflex action takes place. The limb slowly return to its
neutral position. Relaxation phase is prolonged. 587
 E 15.4 PARATHYROID GLAND, VITAMIN D VITAMIN D
N
D PARATHORMONE and Calcium Homeostasis
O ƒƒ MOA : ↑ed calcium absorption from intestine (by indirectly
C ↑ng the level of calcitriol and ↑ed phosphorus excretion.
R ƒƒ PTH and Vit. D3 receptors : are present on osteoblasts.
I ƒƒ Active form of calcium is → Ionized calcium.
N ƒƒ PTH → activates osteoblasts → release IL-1 → Stimulates
O osteoclast to remove Ca++ from bone → hypercalcemia
L ƒƒ Calcitonin receptors are present on osteoclasts (calcitonin
O inhibit osteoclastic activity) → hypocalcemia.
G
Y Features PTH Vitamin D Calcitonin

Secreted by Parathyroid Skin Parafollicular

glands (vit D3), (C-cells) of

/e
Liver (CC) thyroid
Stimulus for ↓ Ca++ ↓ Ca++ ↑ Ca++
secretion ↓ PTH, P
Fig.: The metabolic pathway of Vitamin D

14
Receptors Osteoblasts Osteoblasts Osteoclasts
present on
High-yield Points
Osteoblastic ac- + + -
tivity 44 In tetany hyperexcitability of nerve & m/s is d/to → ↓sed Ca++
which causes ↑es membrane permeability of Na+.
S,
Bone resorption ↑ ↑ ↓
(osteoclast 44 Calcium absorption is facillitated by proteins & acids. Inhibited
inhibition) by phosphates, phytates, oxalates.
Kidney: ↓ ↑ 44 Skin is involved in calcium homeostasis as a source of vitamin D3
AM

PO--4 reabsorpn (phospha- (Cholecalciferol) with the help of UV rays of sunlight.

turic) 44 Index of measurement of bone resorption in urine is Pyridinoline,
Proximal tubular ↑ ↑ ↓ (calciuric) a collagen degradation product.
Ca++reabsorption
Gut: ↑ ↑
HYPOPARATHYROIDISM
O

Ca++reabsorption
Net effect ƒƒ M/c seen following thyroidectomy.
ƒƒ Lab/f – ↓PTH, ↓Serum and urine Ca++, ↑S.PO4– –, ALP
R

Serum calcium ↑ ↑ ↓
(hypoclcemic =N
hm) ƒƒ Cl/f: The signs and symptoms of hypoparathyroidism
Serum phosphate ↓ ↑ ↑ include evidence of latent or overt neuromuscular
hyperexcitability due to hypocalcemia. The effect may be
ƒƒ Calcitonin is a hypocalcemic hormone. It inhibits the aggravated by hyperkalemia or hypomagnesemia.
osteoclasts → thus inhibits bone resorption and also °° Tetany (Erb’s sign), seizures, hyperactive DTRs
↑calcium excretion (calciuric) → hypocalcemia. It is useful °° Trousseau’s sign (carpo-pedal spasm after application
in Paget's d/s, post menopausal osteoporosis, hypocalcemic of cuff)
states (hyperparathyroidism), hypervitaminosis D, °° Tingling of lips/hands, abdominal cramps
osteolytic metastasis. °° Chovstek sign: facial m/s contraction on tapping facial
ƒƒ Parathormone activates Vit D → ↑es Ca++ absorption nerve in front of ear.
from proximal small intestine thus it indirectly ↑ Ca++ °° Paresthesias
absorption . °° Laryngospasm, Bronchospasm
ƒƒ PTH also promotes reabsorption of filtered calcium from °° Prolonged Q-T interval on ECG
proximal tubules of kidney. ƒƒ Basal ganglia calcification and cataract may occur.
588
HYPERPARATHYROIDISM (↑PTH) E
Feature Primary Secondary Tertiary N
D
Serum ↑ N, ↓ ↑
Ca++ O
C
Serum P ↓ + N, ↑ P (↑ALP)
R
ALP ↑ ↑ ↑ I
Causes M/c cause Secondary to In some cases
N
(90%) is renal failure, of 2º H~ O
Single osteomalacia, continuous L
adenoma, rickets, stimulation of O
Multiple malabsorption parathyroid G
adenoma (4%) results in 3º H~
Nodular α1−Hydroxylase
Y
hyperplasia deficiency Fig.: Pseudo-pseudo hypoparathyroidism (PPHP)
(5%)     ⇓
Carcinoma Autonomous Albright's Hereditary Osteodystrophy (AHO)

/e
(1%) hyperactive ƒƒ Found in PHP Ia and PPHP.
chief cells.
ƒƒ Typically patients have short stature, round facies,
Remark m/c Hypocalcemia brachydactyly, obesity, and ectopic soft tissue or dermal

14
parathyroid leads to secondary ossification (osteoma cutis). In the calvaria, this may
disorder stimulation of gland
manifest as hyperostosis frontalis interna.
⇓
Parathyroid gland ƒƒ Intracranial calcification, cataracts and band keratopathy,
hyperplasia, subcutaneous calcifications, and dental hypoplasia.
S,
Hyperphosphatemia
(d/ to renal reten- Osteitis Fibrosa Cystica
tion and ↑ bone
breakdown) ƒƒ Seen in 20 hyperparathyroidism.
AM

ƒƒ Marked osteoclastic activity can be seen and resorbed

ƒƒ 1° hyperparathyroidism is char/by Bones, abdominal bone is replaced by fibrous tissue to produce the so called
groans, psychic moans and renal stones. "Brown tumor" as a consequence of patchy osteolytic
lesions throughout the skeleton and pathological # may
Pseudo hypoparathyroidism (PHP) occur
ƒƒ Resorption affects middle phalanges in hands and alveolar
O

Type Gsa Urine Ca++ PO4 PTH 1, 25 Pheno

defi- cAMP (OH)2 type margins in jaw. Calcilytics are drugs that antagonize the
ciency D calcium-sensing receptor and promote PTH secretion.
R

HP N ↓ ↑ ↓ ↓
PHP Ia 100% ↓ ↓ ↑ ↑ ↓ AHO
PHP Ib 0% ↓ ↓ ↑ ↑ ↓ N
PHP Ic ↓ ↑ ↑ ↓
PHP II 0% N ↓ ↑ ↑ ↓
PPHP Partial N N N N ↓ AHO
(Pseudo-
pseudo)

ƒƒ Pseudohypoparathyroidism (PHP) is d/to end organ/

receptor defect making them refractory to the action of
PTH. 4th and 5th metacarpals may be short.
ƒƒ PTH level is low in HP (hypo), high in PHP (Pseudohypo),
normal in PPHP (Pseudo-pseudohypo). Fig.: Technetium-99m sestamibi scan

589
 E 15.5 ADRENAL HORMONES Hyperaldosteronism vs Addison’s Disease
N ƒƒ Primary hypoaldosteronism is because of autoimmune
D ADRENAL HORMONES destruction of adrenal gland and in India m/c cause is TB.
O
ƒƒ Adrenal cortex secretes 3 major steroids under influence Conn’s Syndrome Cushing’s Synd Addison’s Ds.
C (10 Hyper- (Glucocorticoid (Adrenocortical
R of ACTH.
aldosteronism) excess) insufficiency)
I 1. Mineralocorticoids f rom zona glomerulosa
•• Adenoma is the Iatrogenic steroids Autoimmune/idi-
N 2. Glucocorticoids from zona fasciculata
m/c cause of m/c cause, opathic (m/c) but
O 3. Sex steroids (androgens) from zona reticulata Conn's Pituitary TB is MCC in India,
L [Mn: MGS/GFR] •• B/L cortical hy- adenoma, Amyloidosis, He-
perplasia is the ↑ secretion of mosiderosis.
O
m/c cause of 1o ACTH from Drugs:
G

Cause
High-yield Points hyperaldoster- pituitary Phenytoin,
Y onism. (Cushing’s ds) / Rmp, Opiates,
44 PTH → 84 aa polypeptide.
•• Adrenal Ectopic aminogluthemide,
44 Insulin → 51 aa polypeptide ( a chain 21 a.a & b chain 30 a.a) carcinoma production (Oat KTZ, metyropone,
44 Gluco/Mineralocorticoid, progesterone → 21 carbon steroid. cell Ca) mitotane (medical

/e
44 Androgens (Testosterone, DHT, androsterone, DHEA) → 19 adrenalectomy)
carbon steroid. Exog. steroids
44 Estrogen → 18 carbon steroid. Features of salt/ Features of water Bronze pigmentan

14
44 Androgens (all C-19 steroids) → 17- keto steroid. water retention retention of skin and mu-
44 DHEAs are androgens synthesized from ZR of adrenal gland. Hypernatremia, Moon facies with cosa
Hyperchlorhydria, plethora, (Hyperpigmentan)
Hypervolemia, Buffalo hump, ↓ ECF volume
Hypokalemic Muscle wasting/ Hyponatremia
Glucocorticdids alkalosis weakness, and Hyper
S,
ƒƒ Cortisol (hydrocortisone) is the major glucocorticoid in (episodic Abdominal purple kalemia (meta-
humans. weakness/Tetany) striae, bolic
Hypertension Renal calculi, acidosis)
ƒƒ Receptors are present predominantly in the cytoplasm.
Cl/f
AM

(↑ DBP) HTN Hypoglycemia

Inactive receptor binds with heat shock protein 90. Polyuria, Osteoporosis (↓ Gluconeogen-
ƒƒ Cortisol promotes gluconeogenesis, glycogenesis, Polydipsia Hirsutism, esis)
proteolysis, lipolysis, ↓se lymphocytes, eosinophils, Ankle /pedal amenorrhoea, Calcification of
basophils. [Mn: Steroid cause LEB low] edema not seen Hyperglycaemia, adrenals
ƒƒ Anti-inflammatory action is d/to inhibition of PL- A2. d/to escape Glycosuria, Weakness/
phenomena (Anti insulin asthenia (m/c
O

ƒƒ Glucocorticoids lower → Plasma calcium level.

Alkaline urine effect of ↑ symp)
[Remember all ↑ cortisol) Weight loss
Mineralocorticoids except K+ ] ↓ Na + Cl–
R

ƒƒ Aldosterone is the principal mineralocorticoid. and HCO3–

ƒƒ Mineralocorticoid receptors are expressed in:- Abnormal ACTH stimulation
D/g

°° Mainly in the kidney. Also in colon, salivary glands, dexamethasone test

sweat glands and hippocampus suppression test
{Mineralocorticoid receptors are NOT found in → Surgery, Surgery, IV fludrocortisone
°°
Spironolactone KTZ, metyropone for acute adrenal
Rx

Liver}
insufficiency
ƒƒ Aldosterone regulates minerals ( Na+ and K+) homeostasis.
It acts on principal cells of distal cortical tubules and ƒƒ DOC for suspected adrenal insufficiency is dexamethasone.
collecting duct. ƒƒ DOC for confirmed adrenal insufficiency is hydrocortisone.
ƒƒ ↑es reabsorption of Na+ and also ↑es urnary excretion of ƒƒ Laron dwarfism is due to GH receptor resistance.
K+ and H+. ƒƒ Nelson syndrome is pituitary adenoma after B/l
ƒƒ Aldosterone causes diastolic hypertension without edema. adrenalectomy.
Important negative points: Aldosterone
ŽŽ NOT seen in Primary hyperaldosteronism → Pedal edema.
ŽŽ NOT true about hyperaldosteronism (Conn's syndrome) →
590
Metabolic acidosis.
 CONGENITAL ADRENAL HYPERPLASIA (CAH) E
High-yield Points
ƒƒ Also k/as Adrenogenital syndrome. N
44 Liddle’s syndrome: AD disorder that mimics hyper aldosteronism. D
Defect in sodium channels which leads to continuous activation
ƒƒ More common in females.
ƒƒ M/c cause of CAH is 21a hydroxylase deficiency. AR O
of Na+ –channels leading to increased Na+ absorption in renal
tubules → both renin and aldosterone are low. condition. C
44 Bartter’s syndrome: secondary hyperaldosteronism (d/to high R
renin) but normal BP, no edema. Salt Loosing form Salt Retaining form I
   [Mn: NNN-Normal BP, No oedema, NSAID is t/t]. causes hypotension, shock (causes hypertension) N
21-OH deficiency 11-b(OH) 17-a - OH O
(M/c form 95%, AR) deficiency deficiency L
(also 3b HSD deficiency O
behaves in same fashion;but G
is rare)
** Lipoid enzyme defi.
Y
also has same features but has
opposite effect on genitalia)

/e
Male Female Male Female
Normal Ambiguous Precocious Normal
genitalia but Genitalia puberty genitalia /
  

14
Later (FSH) Precocious
Fig.: Cushing d/s Precocious Puberty
Puberty
Female Male
Pseudoherma- Pseudoherma-
S,
phrodite phrodite
↑b 17-OH-P, ↑ 11–DOCS ↑ DOCS
↑ K+, Met. ↓ 17-OH-P
acidosis
AM

Treat shock Mineralo +

gluco
(FSH = Female pseudo hermaphroditism)

Fig.: Addison's d/s ƒƒ 3-β−HSD deficiency is very rare form. Mild form is a/w
O

precocious puberty, hypospadias in male. Severe form

is salt losing, a/w virlization +, ↓ synthesis of all adrenal
steroids.↑17 OH Pregnenolone and DHEA.
R

High-yield Points
44 21-hydroxylase deficiency is the m/c cause of ambiguous
genitalia in the newborn & m/c cause of CAH.
44 17-hydroxy progesterone (17-OH-P ) in blood & urine is the most
important screening test to diagnose and differentiate various
forms of CAH
44 Prenatal t/t of CAH is possible. At risk pregnant mothers are
started with dexamethasone at 6 weeks of gestation f/b a CVS
at 11-12 week to confirm sex of the fetus. Continue t/t only if the
affected fetus is female, If fetus is male stop t/t.

Fig.: Cushing syndrome
591
 E
N
D
O
C
R
I
N
O
L
O
G
Y

/e
14
S,
Congenital adrenal hyperplasia
21 α hydroxylase deficiency

(A) androgen (C) Cortisol

AM

Male - precocious puberty

A(2)>C(1) Androgen
Female - pseudohermaphrodite, virilism

Salt losing- Na+ Cl- K+

Cortisol
Hypotension
O
R

17 α hydroxylase deficiency

A C

Male - pseudohermaphrodite
A>C Androgen
Female - normal

Salt losing- Na+ Cl- K+

Cortisol
Hypertension

11 β hydroxylase deficiency

A C

Male - precocious puberty

A>C (both are equally raised) Androgen
Female - pseudohermaphrodite, virilism

Salt losing- Na+ Cl- K+

592 Cortisol
Hypertension

This diagram is depicted in simplified manner to explain symptoms only. Biochemical characteristics may differ.