Thyroid hormone functions:

• most metabolic pathways

• Cellular metabolic rate

• Heat production

• Protein, lipid, and CHO meatabolism

• Growth and development

• Rate of synthesis and degradation of other hormones and chemicals

• Stored as thyroglobulin

Iodine/iodide

• food and water provide iodine in form of iodide (I-) or iodate (IO3-)

◦Must be converted in the GI

• <50 mcg/d = hypertrophy and goiter, then low hormone production

• Severe deficiency during pregnancy leads to cretinism

Iodine excess

• Wolff-Chaikoff effect

◦Inhibits thyroid hormone synthesis and secretion

◦Can be used to control thyrotoxicosis until surgery

• May induce hyperthyroidism/AI thyroid disease

• Jod-Basedow effect

◦Smaller iodine amounts in pathology

Synthesis of thyroid hormone

• iodine is trapped across membrane and concentrated in the thyroid follicles by 20-100% over
serum levels by NA/I symporter

• Nutrients helpful for symporter:

◦Vitamin C

◦Activity increased by selenium (but its not a cofactor)

◦B2 aids proper oxidization of iodine in thyroid

• Inhibited by”

◦Reactive halogens (fluorine, chlorine, & bromine)

◦Perchlorates (found in drinking water in CA, New England, IA, TX, IL)

◦Nitrates

◦Possibly flavonoids (quercetin)

◦Inorganic anions (cyanonates, such as thicyante & selanocyanate)

‣ Cherry pits, cherry bark, apricot pits, peach pits, apple seeds, plum pits, elderberry
(seeds, leaves, & stem)

‣ Flax

Damage at the pituitary stalk will DECREASE all anterior pituitary hormones, while INCREASING
prolactin (loss of inhibitory effect of hypothalamic dopamine).

Prolactin

• promotes differentiation of mammary glandular cells and milk production

• Prolactinoma/hyperprolactinemia: symptoms = galactorrhea, amenorrhea, menstrual cycle

dysfunction, possible PMS, associated infertility/PCOS, ovarian cysts, erectile dysfunction,
bilateral breast discharge

• Cushing’s syndrome

Functional hyperprolactinemia treatment

• bromocriptine (dopamine agonist)

• Stress management, aerobic exercise, vegetarian diet, Ca, B6, Mg, GLA, GABA

Medications that may increase prolactin:

• tricyclic antidepressants, OCP’s, estrogen

Anterior pituitary hormones:

• GH

• ACTH

• PL

• FSH

• LH

• TSH

Thyroid

• T3 is active form

• TSH (anterior pituitary)

◦Increased by:

‣ Exercise

‣ Stress

‣ Cold

◦Decreased by:

‣ Light

‣ Melatonin

‣ Corticosteroids

‣ Bromocriptine (dopamine agonist)

◦Best test for primary hypothyroidism

Thyroid function tests:

• fT4

◦Direct measure of free T4

◦Good for monitoring treatment

• fT3

◦Low conversion or T3 toxicosis

• rT3

◦High rT3 may be zinc or selenium deficiency

◦Prolactin increases production of rT3

• Autoantibodies

◦AI dz, such as Hashimoto’s

• Estrogen

◦May cause inaccurate Total T3 or T4 because it increases TBG

• TRH

◦Measures HP axis

HPA axis dysfunction

• stress may:

◦Increase TBG

◦Decrease T4 to T3 conversion

◦Decreases detoxification pathway

Hypothyroid treatment:

• Avoid goitrogens in RAW form (cooked is ok)

• Eat absorbable iodine-rich foods (sea vegetables, sea food, sea salt, protein aids in transport of
iodine)

• Tonify weakened systems: adrenal, GI, comprehensive detox (after stabilizing energy), restore
structural integrity (assess neck MSK)

• Correct nutritional deficiencies: multivitamin, B-complex (AI is often low in B12/folate)

• consider supplementing to promote hormone production (iodine, L-tyrosine) or to provide thyroid

precursors (Fucus, must r/o AI first)

• Alleviate symptoms:

◦Withania somnifera (ashwaganda)

◦Commiphora wightii/mulkul (esp. if dyslipidemia also present)

◦Thyroid glandulars, esp. for AI (stimulates Ab or acts as decoy)

Subclinical/functional hypothyroidism

• Peak incidence in middle age women

• S/s generally milder

• May show as mildly elevated TSH (>2.5), but normal other thyroid levels

• May occasionally have anti-TPO

• May have elevated triglycerides, total cholesterol, and LDL

***increased risk of MI with hypothyroidism

1 grain = 65mg desiccated thyroid (also HCl)

1 grain = 30mcg T4 or 9mcg T3

Wilson’s temperature syndrome

• poor T4 to T3 conversion

• Low body temperature

• May present as chronic fatigue syndrome

• Must have labs to diagnose

• S/s:

◦Fatigue

◦Myofascial pain

◦Depression

◦HA

◦Insomnia

◦Nervousness

• Treatment:

◦Support conversion

◦T3 every 12 hours until body temperature is 98.6 for 3 weeks, stop treatment once
temperature is normal.

Thyroid enlargement

• can happen in hypo and hyper

• Multi nodular = Plummer’s disease

Euthyroid goiter

• labs normal, often after treatment for hyperthyroid

• Probably iodine deficiency

• Lithium can cause

• Common in puberty, pregnancy, and menopause

Hashimoto thyroiditis (AI)

• chronic lymphocytic thyroiditis

• MC cause of primary hypothyroidism in developed countries

• Genetic HLA-B8; HLA-DR 3-5

• Also vitamin D receptor

• Anti-TPO can also bind to adrenal glands, pancreas, and parietal cells in stomach

• May initially start has HYPERthyroid, then euthyroid, the hypo

• Clinical = elevated TSH and high positive anti-TPO, later low free T3 and T4, possibly alkaline
phosphotase

• Abnormal radioactive iodine uptake test

• Treatment:

◦Diet

◦Dysbiosis

◦Food sensitivities

◦Address adrenals

◦DHEA

◦Evaluate environment for hormone disrupters

◦Trace minerals - selenium, zinc, iodine, chromium, manganese (for peripheral thyroid
hormone conversion)

◦Tyrosine (& other AA) to provide hormone precursors and to rebuild GI tract

◦Digestive enzymes

◦Zinc (10-40 mg/d away from other minerals)

◦Iron (12-45 mg/d)

◦Vitamin A (800-3,000 mcg/d)

◦Omega fish oil (2000-4000 mg/d)

◦Vitamin D (4000-5000/d)

◦Adaptogenic herbs

‣ Withania somnifera (100mg)

‣ Glycyrrhiza glabra (adrenal)

‣ Rhodiola rosea (100mg)

‣ Support digestion

• Probiotics 20-50 billion rotate every 3 months for different strains

• L-glutamine (2000-3000mg) heal intestinal permeability and aid cellular repair

• Demulcents (aloe Vera, chlorophyll) calm inflamm and heal mucosa

◦Iris versa color for enlarged gland

Thyroid storm/thyrotoxicosis

• causes

◦Graves

◦Subacute thyroiditis

◦Toxic multi nodular goiter

◦Thyroid hormone excess (from medication)

◦Toxic adenoma/carcinoma

 ◦Excess TRH

◦Hydatiform mole

◦Usu age 20-40

◦Smoking, lithium, and iodine containing meds (amiodarone)

◦Corticosteroid withdrawal

◦Recent pregnancy

• Genetic HLA-B8, HLA-DR3 = Caucasians; HLA-Bw46 and HLA-B5 in Chinese

Graves’ disease

• s/s

◦Fatigue

◦Weakness

◦Photophobia

◦Eye sensitivity

◦Dry eyes

◦Ocular pain

◦Diplopia

◦Blurred vision

◦Neck ache

◦Insomnia

◦Nervousness/irritability

◦Emotional lability - rapid, often exaggerated changes in mood

◦Change is texture of skin & nails

◦Change in temperature preference

◦Increased appetite

◦Dyspnea

◦Palpitations (r/o MI with last 2 symptoms)

◦Vitiligo

◦Increased perspiration

◦Goiter

◦Ankle edema

◦Tachypnea and tachycardia

◦Weight loss

◦DECREASE in menstrual flow and/or cycle

◦Hyperreflexia

◦Exopthalomos

◦Lymphadenopathy

• Can use NO SPECS to “grade”/screen for Graves

◦N (no physical signs or symptoms) = 0

◦O (only signs, no symptoms = limited to upper lid retraction, lid lag, and proposes up to
22mm) = 1

◦S (soft tissue involvement, signs & symptoms) = 2

◦P (proptosis) = 3

◦E (extraoccular muscle invovlement) = 4

◦C (corneal involvement) = 5

◦S (sight loss - optic nerve involvement) = 6

• Clinical

◦Low TSH

◦High free T4 and free T3

◦Normocytic anemia

 ◦Mild leukopenia

◦High all phos, liver function tests, and serum calcium

◦Elevated Ab = TSI (thyroid stimulating immunoglobulin), has MANY names, TSH-R, TRAb,
etc.

• Conventional treatment

◦Methimazole or propylthiouracil (PTU) = anti-thyroid

◦Beta blockers = blocks of T3 - T4

◦Corticosteroids = reduces conversion of T3 to T4, suppresses thyroid stimulating Ab

◦Perchlorate = Iodide transport blockers (side effect = aplastic anemia)

◦Iodide loading = high doses inhibit iodide formation and block hormone release (SHORT
TERM ONLY) = Lugols and Saturated solution of potassium iodide

◦Sub or total thyroidectomy

◦Thyroid or radioactive iodine abalation

• Other treatment/support

◦Minimize obstacles to healing/re-establish healthy lifestyle

‣ Sleep/wake cycle

‣ Stress management

‣ Mild activity

‣ Avoid stimulants

◦Stimulate the vis

‣ Cold compress over thyroid

‣ Constitutional hydrotherapy

‣ Acupuncture

‣ Homeopathy

◦Emphasis goitrogens (2-3 servings /d)

◦Emphasis non-GMO foods and isoflavones containing foods

◦Address food sensitivities

◦Tonify weakened systems

‣ Nervine/adrenal

‣ Fish oil, CoQ10

‣ Immune modulation

‣ Restore structural integrity

◦Correct nutrient deficiency

‣ B-complex

‣ Ca

‣ Antioxidants

‣ Hesperides

‣ Selenium

• Alleviate symptoms

◦Nervine: valerians, passiflora, scutellaria

◦Melatonin (suppresses T4 production)

◦Anti-thyroid: Melissa, Leon Russell, lycopus

True thyroid storm is medical emergency!

• Treatment

◦Rest, mild sedation

◦Fluid/electrolyte replacement

◦O2 therapy

◦High dose PTU

◦Iodide loading

 ◦Beta blockers and corticosteroids

Subacute/De Quervain’s thyroiditis

• granulomatous condition

• Usu Hx of URT viral infx (MC is staph aureus)

• Giant cell infiltration

• Clinical

◦Sore throat followed by progressive

◦Tenderness in neck (bilateral, moving to unilateral, worse swallowing or turning head)

◦Low grade fever

◦Thyroid is asymmetric, firm, tender

◦Low RAI uptake (if done)

◦First few weeks

‣ High ESR, CRP, and free T4

• Can reoccur or cause permanent hypothyroid

• Self-limiting (usu) so managed w/ corticosteroids, analgesics, NSAIDS

• Naturopathic treatment

◦Avoid immune suppression and iodine

◦Anti-viral herbs

◦Vitamin C, zinc

◦Stress reduction, rest, and sleep

◦Hypoallergenic diet

◦Short term use of thyroid hormone replacement

Postpartum thyroiditis

• thought to be AI

• Can present like hypo - high 1st, then low

• Usu self-limiting (~1yr)

Toxic multi nodular goiter

• secretes excess thyroid hormone

• Presents like hyperthyroid, but w/o eye symptoms

• Enlarged multi nodular goiter

• Low TSH, high free T3

• Avoid excess iodine

• Treat like Graves

Hyperthyroidism in pregnancy

• most 2˚ to Graves

• Increases risk for heart failure, preeclampsia, premature labor, low birth weight, perinatal
mortality, congenital anomalies

• If high dose iodine given baby can be born w/ goiter

Painless/silent thyroiditis

• presents like hypothyroidism

• Self-limiting

Part 2

Adrenal glands
• Upper poles of kidneys

• 10 g = normal weight

• 90% = outer cortex

◦Glucocorticoids

‣ ACTH and CRH (aka CRF) regulate secretion

• Secreted in a pulsatile fashion with a circadian rhythm

◦Levels are highest on waking

‣ Stimulated by stress

• Physical and psychological

• Exercise

◦Cortisol is elevated for at least 40 minutes

• Hypoglycemia

‣ 75% bound to corticosteroid-binding globulin

‣ 15% bound to albumin

‣ 10% unbound

‣ 95% conjugated by liver and excreted in urine

◦Regulation of cortisol: (HPA axis)

‣ Diurnal (24 hour cycle - circadian)

‣ Stressors:

• Hypoglycemia

• Hypotension

• Fever

• Trauma

• Surgery

‣ (HPA axis) Hypothalamus releases CRH which acts at the anterior pituitary -> in
response to CRH the anterior pituitary synthesizes and releases ACTH -> ACTH acts on
the cortex of the adrenals to release cortisol

• Effects of cortisol on metabolism:

◦Increased gluconeogenesis and glycogenolysis

◦Increased proteolysis and lipolysis

• Effects of cortisol on cardiovascular system:

◦Increased myocardial contractility

◦Increased cardiac output

◦Increased catecholamine pressor effect

◦Mineralcorticoids (aldosterone)

‣ Promote:

• Retention of sodium (by the kidneys)

• Renal excretion of potassium

• Increase of plasma.Na/K ratio

• Alkalosis

• Increase in circulating blood volume

• Increase in blood pressure

‣ Renin-angiotensin system and ACTH regulate secretion of aldosterone (blood pressure)

• Renin from kidneys meets angiotensinogen from the liver in the bloodstream to
form Angiotensin 1

 ◦Regulation of RAAS

‣ ACTH is an ACUTE regulator of RAAS, which is normally regulated by

potassium and angiotensin 2. ACTH interacts with G-protein coupled
hormone receptors. This in turn activates cAMP/PKA pathway thereby
regulating intracellular calcium flux and CYP11B2 transcription, which is
the specific steroidogenic enzyme of aldosterone synthesis.

• ACE (angiotensin-converting enzyme) from the lungs meets angiotensin 1 to form

angiotensin 2

◦Angiotensin raises BP by:

‣ Vasoconstriction

‣ Sympathetic nervous stimulation

‣ Increased aldosterone synthesis

‣ Renal actions

◦Angiotensin other actions:

‣ Induction of growth

‣ Cell migration

‣ Mitosis of vascular smooth muscle cells

‣ Increased synthesis of collagen type I and III in fibroblasts (thickening of

vascular wall and myocardium

‣ Fibrosis

◦Androgens (DHEA, testosterone, and androstenedione):

‣ Pregnenolone is the precursor to ALL androgens and cortisol.

• Synthesized from cholesterol and in adrenals.

‣ DHEA-S (sulfate) is from adrenal cortex, most is from here.

• Other source is ovaries/testes

‣ Transported by sex hormone-binding globulin (SHBG)

‣ PCOS - one hypothesis is hyperandrogenic oligoovulation

• 10% = medulla

◦Catecholamines: EPI (80%) and NE (20%)

‣ Neurotransmitters in postganglionic sympathetic NS

‣ EPI is triggered by stress (fight, flight, or freeze)

‣ Can be produced from NE by enzyme PNMT, whose production is induced by cortisol

• General adaptation syndrome (GAS):

◦Hypothesis that adaptive response to stress through adrenals leads to allergies, chemical
sensitivity, and ulcers.

• Maladaptive Stress Syndrome (Clinical model of GAS):

◦4 stages:

‣ Stage 0:

• Healthy adapted states from hypovigilance to hypervigilance, properly mediated by

ANS, adrenal hormones, and catecholamines .

• Stimulants increase vigilance (coffee, tea, nicotine, etc.)

• Relaxants decrease vigilance (alcohol, opiates, cannabis, etc.)

‣ Stage 1 - Alarm phase:

• Chronic excess production of catecholamines.

• Increase in production of glucocorticoids

◦Response:

‣ Sympathetic NS is in flight/flight mode.

◦Result:

‣ Feelings of anger, anxiety, etc.

‣ Palpitations

‣ Insomnia

 ◦Treatment:

‣ Determinants of Health:

• Rest/sleep

• Meditation and prayer

• Light/air (Go outside!)

• Hydration/diet

‣ Replace depleted nutrients:

• Pantothenic acid (B5) with Vit. C

• Melatonin (short term!)

‣ Nervines:

• Scutellaria (skullcap)

• Passiflora (Passionflower)

• Piper methistycum (kava) - physical relaxation

• Valeriana officinalis (Valerian) - mental relaxation

‣ Cortisol antagonist:

• DHEA

‣ Stage 2 - Suppression Phase: (Cushing’s, Pseudo-Cushings’s, Subclinical Cushing’s,

Adrenal Insufficiency)

• Chronic excess production of cortisol.

• Increase in production of catecholamines

• Increased mineralcorticoids?

◦Response:

‣ Suppressed immune system

‣ Increased inflammatory response

◦Result:

‣ Infections

‣ Depression

‣ Gastritis/ulcers

‣ Hyperlipidemia/atherosclerosis

‣ Osteoporosis

‣ DM/degenerative disease

‣ Hirsutism (from increased androgens, d/t increased cortisol)

‣ And so much more...

◦Treatment:

‣ Determinants of Health:

• Rest/sleep

• Meditation and prayer

• Light/air (Go outside!)

• Hydration/diet

‣ Cortisol management:

• DHEA (cortisol antagonist) - balance cortisol

• Withania somnifera (Ashwaganda) - decrease cortisol

‣ Targeted treatment:

• Hypericum perforatum (St. John’s wort) or tyrosine for depression

• Taraxacum officinale (dandelion) for edema

• Chromium for blood sugar regulation

• Serenoa repens (saw palmetto) for androgen excess

‣ Stage 3 - Exhaustion Phase: (Pseudo-Addison’s)

• Chronic decrease in production of corticosteroids.

• Chronic decrease in production of mineralcorticoids.

• Chronic decrease in adrenal androgens.

 • Intermittent excess secretion of catecholamines.

◦“Riding on catecholamines”

◦Response:

‣ Immune deficiency

‣ Environmental sensitivities

‣ Poor resistance to stress

◦Result:

‣ Hypotension (postural)

‣ Functional hypoglycemia

‣ CFS/fibromyalgia

‣ Anxiety/depression

‣ And so much more...

◦Treatment :

‣ Determinants of Health:

• Rest/sleep

• Meditation and prayer

• Light/air (Go outside!)

• Hydration/diet

‣ Cortisol management:

• DHEA (cortisol antagonist) - balance cortisol

• Glycyrrhiza - increase cortisol (inhibits 11-beta-hydroxysteroid

dehydrogenase type 2 and 5beta-reductase, also upregulates Na+
reabsorption and K+ secretion)

‣ Detoxification

• Carefully!

‣ Targeted treatment

‣ Adrenal glandular

• Not always advisable, must be done properly/carefully, as many

patients don’t respond well.

• Only from a trusted compounding source to ensure proper dose and

be sure of purity/quality.

• Cortical Hyperfunction:

◦Can be pituitary or ectopic.

◦Cushing’s Syndrome

‣ Most common cause is iatrogenic (steroid use).

‣ Classified as:

• ACTH Dependent

◦Cushing’s Disease (pituitary adenoma) - secretes ACTH

‣ 5:1 female:male ratio

‣ Average age of diagnosis is 20-40, but can be diagnosed at ANY age.

◦Ectopic ACTH Syndrome - non-pituitary neoplasm (lung cancer)

◦Ectopic CRH Syndrome - non-pituitary neoplasm (lung cancer)

• ACTH Independent (outside of HPA axis)

◦Exogenous glucocorticoid therapy

◦Adrenal adenoma

◦Adrenal hyperplasia

‣ Signs/symptoms of Cushing’s Syndrome:

• Truncates obesity with slender extremities

• Moon facies

• Easy bruising

• Poor wound healing

 • Alopecia

• Renal stones and HTN (aldosterone/mineralcorticoids overlap)

• Menstrual disorders

• Skin thinning/connective tissue weakness

◦Leads to purple striae

• Muscle wasting

• Supraclavicular and dorsal fat pads (Buffalo hump)

• Glucose intolerance

• Osteoporosis - RISK FACTOR for both exogenous AND endogenous cortisol

• Virilism

◦***Don’t forget excess cortisol effects aldosterone

◦Laboratory testing for hyperadrenocorticism:

‣ Combination of tests must be used.

• CMP

◦Serum Na+ tends to be high

◦Serum K+ tends to be low

◦Na/K ratio is high (>40:1)

‣ Aldosterone increases Na+ resorption and decreases excretion.

• CBC

◦Eosinophils may be low

• Cortisol (serum, urine, saliva)

◦Tends to be high, 24-hr cortisol abnormal

◦urine free cortisol correlates w/ high cortisol levels.

• Abnormal:

◦Dexamethasone suppression tests

◦Metyrapone

◦CRH

◦CT or MRI

◦Adrenal reactive uptake

• 17-hydroxy-corticosteroids will be abnormal

• Insulin tolerance test

• Androgens will be abnormal

◦Should evaluate for DM, menstrual irregularities, and osteoporosis when indicated

◦Treatment for Cushing’s syndrome:

‣ Determinants of health

‣ Stop smoking (raises cortisol and lowers androgens)

‣ High protein, anti-inflammatory diet

‣ And adequate hydration

‣ Exercise

‣ Sleep and relaxation

‣ Address nutrient deficiencies:

• Fish oil

• Vitamin C (1,000mg TID)

• Zinc (15mg BID w/food)

• Magnesium (150mg TID)

• B5 (500mg BID)

• Alpha-lipoic acid (R form 150mg TID) w/ milk thistle

• Phosphatidyl serine (decreases plasma cortisol and ACTH)

• Melatonin

• Anti-inflammatories

• Adrenal glandular

 ‣ Botanicals:

• Withania somnifera (Ashwaganda)

• Magnolia officinalis

• Eleutherocccus senticosus (Siberian ginseng root)

• Ocimum sanctum (holy basil)

• Schisandra

• Immune, CV support, blood sugar, connective tissue, liver support, etc.

• Cortical Hypofunction (Addison’s)

◦Low/suppressed ACTH production

◦Types:

‣ Primary is Addison’s Disease

‣ Secondary is adrenal insufficiency (ACTH deficiency)

‣ Tertiary is adrenal insufficiency (CRH deficiency)

‣ Autoimmune Adrenocortical Insufficiency:

• Most common

• Associated with DM1, AI thyroid disease (also alopecia areata, primary

hypogonadism, pernicious anemia, and celiac disease.)

◦Functional can be triggered by stress/trauma (see Maladaptive Stress Syndrome above)

◦Iatrogenic caused by improperly discontinuing corticosteroids

◦Clinical presentation:

‣ Weakness and fatigue

‣ Anorexia -> weight loss

‣ Hyperpigmentation

‣ Hypotension

‣ GI disturbances

‣ Salt cravings

◦Signs/symptoms:

‣ Weakness (asthenia), better with rest

‣ Fatigue, worse for >24 hrs after activity

‣ Cold intolerance

‣ Apathy, depression, poor stress response

‣ Anorexia

‣ Smell & taste sensitivity

‣ Multiple chemical sensitivities

‣ Low basal body temperature (BBT)

‣ Sodium depletion

‣ Orthostatic hypotension

‣ Reactive hypoglycemia

‣ Hyper-pigmentation (pressure-points, skinfolds, Arellano, perineum, mouth)

‣ Vitiligo

‣ Weight loss

◦Assessment:

‣ Primary Addison’s

• ACTH elevated

• ACTH stimulation, abnormal

‣ Secondary Addison’s

• CRH stimulation, abnormal

• Low 24 hr cortisol

• Low DHEA (and probably all androgens)

• Na/K ratio <30

◦If K is >4.5, along with a normal or low Na.

 • Elevated eosinophils

• Elevated BUN and BUN/creatinine ratio

• High renin

• Low aldosterone

◦Treatment:

‣ Find underlying cause:

• Systemic disease, chronic infection, past steroid use, functional hypoglycemia.

‣ Determinants of health:

• Graduated moderate exercise

• Sleep

• Light

• Relaxation

‣ Hypoglycemic diet

• Limit sugars and carbohydrates

• Frequent meals

‣ Adequate fluids

‣ Address nutrient deficiencies:

• Vit C, B5, B12, EFA’s, amino acids, antioxidants

‣ Immune support

‣ AVOID DHEA
‣ Pregnenolone (10-50mg HS) (HS = at bedtime)

‣ Adrenal glandular

◦Conventional treatment:

‣ Hydrocortisone 30mg QD

‣ Fludrocortisone 0.1 - 0.2 mg QD

• Adrenal crisis (emergency!)

◦Clinical presentation:

‣ Hypotension -> shock

‣ Fever

‣ Dehydration -> volume depletion

‣ Nausea, vomiting, and/or anorexia

‣ Weakness, apathy, depressed mentation

‣ Hypoglycemia

◦Treatment:

◦IV cortisol and fluids, based on body weight

Hyperaldosteronism
• Primary (Conn’s syndrome):

◦Usually from a tumor, adenoma of adrenal cortex, unilateral or bilateral adrenal hyperplasia,
or carcinoma.

• Secondary hyperaldosterone:

◦Increased aldosterone secretion that occurs secondary to a known stimulus

‣ Example: activation of the RAS

• Signs and symptoms:

◦HTN

◦Polyuria

◦Polydipsia

◦Alkalosis

◦Weakness

◦Paraesthesias

◦Tetany

 ◦Transient paralysis

◦High serum Na and Cl

◦Low K and Mg

• Screening guidelines from endocrine society:

◦1. Sustained BP >150/100 despite:

‣ 3 anti-HTN and a diuretic, or

‣ 4 anti-HTN

◦2. HTN with hypokalemia

◦3. HTN with adrenal nodule

◦4. HTN with obstructive sleep apnea

◦5. HTN with family history of stroke at a young age

◦6. All primary relatives of patient diagnosed with primary aldosteronism

• Assessment:

◦Plasma aldosterone/renin ratio >40

◦24 urine aldosterone

◦Saline loading test

◦CT scan

◦Bilateral adrenal vein sampling (requires a specialist.)

• Treatment:

◦Primary aldosteronism - conventional support

‣ Surgery if adenoma.

‣ Spironolactone to treat HTN d/t to aldosterone

• 1st doses 100-400mg are used, but in general 25mg

‣ Resolve underlying conditions while using supportive care.

‣ Replace nutrients:

• Potassium, B6, Vit. C

‣ Diuretic and anti-HTN botanicals:

• Taraxacum leaf

• Urtica

• Crataegus

• Tilia

• Allium sativa

• NOTE: sometimes lowering BP by one mechanism “angers” another disease

process. (Salt restriction -> insulin resistance).

Hypoaldosteronism
Deficient mineralcorticoid production or action. Aldosterone release from the adrenal gland may be
reduced by:

◦Primary hypoaldosteronism

◦Hyporeninemic hypoaldosteronism

‣ Most common in elderly patients with diabetes and mild renal insufficiency.

◦Isolated deficiency of ACTH (secondary hypoaldosteronism)

◦Associated with Addison’s, polyglandular endocrinopathy, HIV, or TB.

Pheochromocytoma
Catecholamine-producing tumors derived from sympathetic or parasympathetic nervous system.

• Tumor of chromaffin cells of adrenal medulla or extra-adrenal

• Higher degree of malignancy

◦May occur as part of Multiple endocrine syndrome (MEN)

◦With thyroid cancer, parathyroid neoplasia (Sipple’s syndrome)

• Signs and symptoms:

◦HTN

 ◦Tachycardia

◦Tachypnea

◦Excessive sweating

◦Flushing

◦Headache

◦Anxiety

◦NOTE: However, the clinical presentation is highly variable and so pheochromocytoma has
been dubbed “the great masquerader”.

• Assessment:

◦High 24 hour epinephrine, vanillylmandelic acid, or homovanillic acid.

◦Urine collection for VMA, HVA, and metanephrines.

◦CT or MRI for adenoma

• Treatment :

◦Rauwolfia serpentina

◦Metyrosine (inhibits NE production)

◦Alpha and beta adrenergic blocking agents

◦Surgical excision

◦Chemotherapy for malignancy

• Two types of 21-hydroxylase deficiency:

◦Classic salt wasting

‣ Reduced aldosterone, cortisol, Na, and K.

‣ Increased testosterone and renin.

‣ 17-CHP >5,000mg/dL

‣ Diagnosed from newborn to 6mo.

◦Simple virilizing

‣ Normal aldosterone

‣ Reduced cortisol

‣ Increased or normal renin

‣ Increased testosterone

‣ 17-CHP 2,500 - 5,000mg/dL

‣ Diagnosed from newborn to 2yrs in females, 2 - 4yrs in males.

Congenital Adrenal Hyperplasia (classical type)

• Group of disorders that results from one of several enzymatic defects in steroid metabolism.

◦Mutations in CYP21A2, CYP11B1, CYP17, and 3betaHSD - genes that encode for enzymes
and sTAR protein.

◦Absence of enzymes leads to decreased conversion of 17-hydroxyprogesterone to 11-

deoxycortisol = result is cortisol deficiency.

• Deficiency of steroid 21-hydroxylase most common.

• Mineralcorticoids low, sex hormones increased

• Most common cause of ambiguous genitalia in females.

◦Autosomal recessive, 1 in 15,000 births.

• US tests for at birth.

• Symptoms (starts in 2nd week of life):

◦Lethargy

◦Irritablility

◦Poor feeding

◦Vomiting

◦Poor weight gain

◦Later there may be virilization (similar to hirsutism) of prepubertal children.

Nonclassical Adrenal Hyperplasia

Called late-onset CAH, adult-onset CAH, or the attenuated form of CAH, milder form of CAH from
deficiency of steroid 21-hydroxylase.

◦Usually hirsute female patient presenting with infertility.

◦Must consider in PCOS patients.

◦Normal aldosterone, cortisol, and electrolytes, may have elevated androgens.

Macronodular Adrenal Hyperplasia

Thought to result from long-standing adrenal ACTH stimulation, which leads to autonomous adrenal
adenoma formation.

Male Hormones
Testes

◦3.5 - 5cm side

◦12 - 25 mL volume

◦Produces hormones

‣ Androgens

‣ Spermatozoa

◦Seminiferous tubules

‣ Produce spermatozoa

‣ Sertoli cells

• Produce:

◦Androgen-binding protein (ABP)

◦Dihydrotestosterone

◦Leydig cells

‣ Interstitial cells between the seminiferous tubules

Androgens

◦Cholesterol -> Pregnenolone -> progesterone -> then

‣ Androgens (DHEA, androstenedione, testosterone, DHT)

‣ Estrogens (E1, E2, and E3 - placenta only) = prostatic growth in males, so excess
causes hyperplasia.

‣ Steroids (cortisol, cortisone, aldosterone)

◦DHEA from testes

◦DHEA-S from adrenals - more common

◦Androstenedione and androstenediol (intermediates)

◦Testosterone (5 alpha reductase) then Dihydrotestosterone (DHT)

‣ Negative feedback to GnRH and LH

‣ Released every 20 minutes

‣ 5 - 7 mg produced daily

• Peak levels at 8am, lowest at 8pm

‣ 30 - 40% bound to SHBG

• Can be tested.

‣ 60 - 70% bound to albumin and plasma proteins

‣ ~2% free testosterone

◦Actions:

‣ Sexual development - male secondary sex characteristics

‣ Skin and hair

‣ Libido and erectile function

‣ Sperm production

‣ Bone and muscle

‣ Behavior and cognition

 ‣ Gonadotropin secretion

‣ CV protection, but only when in correct amounts

◦Drugs that adversely affect endocrine testicular function:

‣ Cimetidine - competitive antagonist of androgen receptor

‣ Ketoconazole

‣ Hmg-CoA reductase inhibitors

‣ Pioglitazone - hypoglycemic agent

‣ Antiepileptic drugs

‣ Amiodarone

‣ Digoxin

‣ Cannabinoids - daily use can cause infertility d/t low sperm count

‣ Heroin and methadone

‣ Alkylating agents (chem and radiation)

‣ Radioiodine

‣ Androgens steroids - results in rapid and profound suppression of LH, that may persist
after withdrawal

• Low SHBG

• History of of at-risk activity

‣ Spironolactone - steroid analogue that binds to mineralcorticoid and androgen

receptors.

◦Hormones of importance:

‣ Prolactin - elevations in serum prolactin inhibit normal release of pituitary gonadotropins

in men.

‣ FSH - sperm response

‣ Testosterone, dihydrotestosterone, and estradiol are important for proper male

reproductive function.

◦Vitamin and minerals related to testosterone:

‣ Zinc - deficiency lowers testosterone by not inhibiting prolactin secretion (prolactin

inhibits testosterone)

‣ Magnesium - makes testosterone more biologically active.

‣ Carnitine - boosts dopamine, which is directly related to testosterone levels, may also
prevent testosterone decline from physical stress.

‣ Folate - deficiency reduces circulating testosterone.

‣ Vitamin C - protects prostate from testosterone-induced tumors.

‣ Vitamin B6 - regulates sex hormones by reducing prolactin and is also a cofactor for
dopamine synthesis.

‣ Vitamin D - regulates the synthesis of testosterone.

‣ Vitamin K - deficiency reduces testosterone production, a rate-limiting enzyme

(Cyp11a) for testosterone is Vitamin K dependent.

‣ Vitamin E - long tern use may reduce testosterone levels.

Hypogonadism
A clinical syndrome the results from failure of the testis to produce physiological levels of
testosterone and the normal number of spermatozoa caused by a disruption of one or more levels
of the hypothalamic-pituitary-testicular (HPT) axis.

• Types of hypogonadism:
◦Primary (hypergonadotropic hypogonadism) - gonadal failure

‣ Impaired spermatogenesis

‣ Excess pituitary gonadotropin secretin and levels

◦Seconadary (hypogonadotropic hypogonadism) - pituitary Oregon

‣ Low FSH

 ‣ Low LH
◦Tertiary - hypothalamic origin

‣ Low FSH

‣ Low LH

‣ Low GnRH
◦Compensated - unknown etiology

‣ Age-related subclinical hypoandrogenism

‣ Testosterone normal

‣ Estradiol high

• Signs and symptoms - no unique symptoms, use ADAM screening

• ADAM screening:

◦Do you have a decrease in libido?

◦Do you have a lack of energy?

◦Do you have a decrease in strength and/or endurance?

◦Have you noticed a decreased “enjoyment of life”?

◦Have you lost height? (feet have flattened)

◦Do you have to shave less?

◦Are you sad and/or grumpy?

◦Are your erections less strong?

◦Are you falling asleep after dinner?

◦Has there been a recent decrease in your work performance?

• Sexual dysfunction in hypogonadism:

◦NO production - vascular tissues have androgen receptors.

◦Low testosterone - reduced neuronal growth

◦CNS signaling - androgen receptors in hippocampus, amygdala, thalamus, cerebellum,

olfactory bulb.

• Clinical manifestations of hypogonadism:

◦Physical/metabolic

‣ Fractures d/t decreased bone mineral density

‣ Decreased muscle mass and strength

‣ Gynecomastia

‣ Anemia

‣ Frailty

‣ Increased body fat/BMI

‣ Insulin resistance

‣ Vasomotor instability - aka hot flash and/or temperature alterations

◦Psychological

‣ Depressed mood

‣ Diminished energy, sense of vitality, or well-being

‣ Impaired cognition and memory

◦Sexual

‣ Diminished libido

‣ Erectile dysfunction

‣ Difficulty achieving orgasm

‣ Decreased spontaneous erections

• Primary causes:
◦Orchitis (from mumps)

◦Gonadal radiation

◦Cryptoorchisim

◦Gonadal neoplasm

◦Testicular agenesis

 ◦Kallman’s syndrome

◦Klinefelter’s syndrome

◦Prayer-Willi syndrome

◦Sertoli cell only syndrome

◦Myotonic dystrophy

◦Leydig cell failure

◦LH receptor defects

• Secondary causes:
◦Side effects of medication

◦Pituitary tumors, radiation, or surgery

◦Panhypopituitarism

◦Genetic

◦Kallman’s Syndrome

◦Prayer-Willi syndrome

◦Laurence-Moon-Beidl syndrome

◦FSH or LH only deficiency syndromes

◦Decreased HPA axis responsiveness, from gradual decline in testicular function

• Other causes:
◦Obesity/metabolic syndrome

◦Malnutrition/eating disorder

◦Excess alcohol, marijuana, and/or cocaine use

◦Chronic illness

◦Adrenal insufficiency/chronic stress

◦Medications:

‣ Spironolactone

‣ Digoxin

‣ Cimetidine

‣ Antidepressants

◦Depression/mood disorders

◦Hemochromatosis

◦Vigorous athleticism

• Hypogonadism assessment:
◦Basic labs: CBC, CMP, PSA

◦Serum LH, FSH, and prolactin

◦Androgens: serum testosterone, DHEA (both)

‣ Total testosterone can be used to diagnosis hypogonadism

‣ Low androgens without gonadotropin elevation suggests hypogonadotropic

hypogonadism