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Three fxs of Prolactin

Breast development; Milk production; Sexual gratification

LH fxs

Females: Triggers ovulation, Devt of corpus luteum;
Males: Production of testosterone by Leydig cells

FSH fxs

Females: Follicle growth and oogenesis;
Males: Spermatogenesis

ACTH fx

Stimulates Adrenal cortex to release the cortical triad: Aldosterone, Cortisol, Androgens

GH (STH) fx

Stimulates growth/mitosis/protein synthesis at bones, muscles

IGF-1 origin & fx

Made at liver, mediates (and is agonist for) GH effects

Four Oxytocin fxs

Cervical dilation, Uterine contractions, Milk let-down, Neurotransmitter

ADH fx

(vasopressin): Anti-diuresis (H2O reabsorption) & vascular constriction

Pituitary masses

Most are benign but many secrete 1 or more hormones; 10% of all reported intracranial masses; ≤25% pop

Microadenoma vs macroadenoma

≤1cm X ≥1cm

Most common pituitary adenomas, effect, gender distribution

Prolactinomas; hyperprolactinemia/gynecomastia; mostly female

Symptoms of Hyperprolactinemia

Galactorrhea, Breast enlargement & tenderness, Anovulatory amenorrhea, dysmenorrhea, Decreased libido, ED

Hyperprolactinemia Tx

Bromocriptine (Parlodel- a DA agonist) or Cabergoline (Dostinex- an ergot derivative used to Tx Parkinson's, associated w/ gambling compulsion)

Bromcriptine use; Trade; Mechanism; Contraindications

Dopamine agonist used in the treatment of pituitary tumors, Parkinson's, Hyperprolactinaemia, Neuroleptic Malignant Syndrome, and DM2. For Hyperprolactinemia, given as PARLODEL; Decreases Prolactin; CONTRAINDICATED in BREASTFEEDING

Bromcriptine Iax

Triptans (serotonin receptor agonists in migraine Tx), Decongestants (HTN/tachy), Antipsychotics (hTN)

Cabergoline use; Trade; Mechanism; Contras

Hyperprolactinemia Tx (Dostinex); DA agonist @ Ant Pit, decreases Prolactin; Contraindicated in Breastfeeding

Short Stature Dx

2 SDs below average for age/gender;
Gold STD: Insulin tolerance (0.1ug/kg) followed by sampling for GH. If GH <5 (10 in kids) POS for GH deficiency

Short stature Tx; Iax's,SEs

GH daily injection: Nutropin, Humatrope, Genotropin; Increase [glu], decrease INR in Coumadin pts; Diabetes, HTN, Pancreatitis

Acromegaly Dx; Tx; SEs

GH levels 1 hr after1 hr-GTT are >1µ/L;
Surgical resection & Octreotide IM (Sandostatin) or Lanreotide IM (Somatuline);
Cardiomegaly/CHF, HTN, Diabetes/RF, HA/visual disturbance from tumor

Thyroxine forms & distribution

T4: 90%, T3: 10% (4X [T4]); 99% is bound to TBG (Thyroid Binding Globulin); ONLY FREE hormone is ACTIVE

Element required for thyroxine

Iodine

Cells producing T4 & mechanism

Follicular cells; bind I to Thyroglobulin (TG)

Iodine-capturing enzyme

Thyroid Peroxidase TPO)

Thyroxine regulating gland & hormone; regulatory mechanism

TSH (Thyrotropin) made at Ant Pit in response to T4 levels

Second Thyroid hormone & fn

Calcitonin, Ca2+ regulator (opposes PTH-- decreases serum [Ca2+]

Hypothyroid S/s

Fatigue, Wt gain, Depression, Hair loss, Dry skin, Dysmenorrhea, Brady

Hypo-Iodine incidence

9% omnivores, 25% vegetarians, 80% vegans are LOW

Hashimoto's; Gender distribution; Mechanism

Autoimmune hypothyroidism; 10X more female; Thyroid Peroxidase ABs bind & inhibit T4; Insidious onset w/ hyPER-thyroid 1st; Hi Genetics

Hashimoto's Labs

TPO-AB & TSH elevated, T3/T4 depressed

Myxedema S/s

Non-pitting edema w/ severe hypothyroidism, Reduced CO, Mental slowing--> myxedemic coma ppt'd by stroke/MI

Hypothyroidism Tx & Allergic issue; alternative

Levothyroxine (LT4) (Synthroid or Levothroid); Made w/ lactose binder OR
Dessicated Thyroid (porcine or bovine)

Thyroid Replacement Monitoring

Monitor TSH, also T3/T4;
NB: T3 replacement suppresses TSH

Grave's Dz; S/s

Autoimmune Hyperthyroidism [Agonist effect]; Nervous, Tachy, Weight loss, Exophthalmia, Hyperhidrosis, Tremor, Insomnia

Grave's Rxs names, mechanism; side effects

Methimazole and Propylthiouracil; Inhibit addition of iodine to Thyroglobulin to block T4 synthesis; Leukopenia, Agranulocytosis, Aplastic Anemia; Hepatotoxicity (PTU also alters INR in Coumadin Tx

1st line Grave's Tx

Methimazole (Tapazole), Propylthiouracil (PTU)

2nd line Grave's Tx

Ablation (w/ I-131) or thyroidectomy, followed by thyroid replacement Tx

Acute Thyroiditis Dx & Tx

Hyperthyroidism secondary to infection. Differentiate from Grave's by radioactive I uptake [I-131 uptake by Grave's is high, uptake by Acute [=Toxic] Thyroiditis is low; treatment for acute is oral steroids

How Thyroid masses are evaluated

40-50% adults; Usually benign tumors but may be cysts [rare]; Ultrasound to ID [Gold Standard], Cysts usually resolve, but may needle aspirate

Thyroid nodule Diagnosis & Treatment

Ignore unless >1.5 cm, then aspirate and/or treat with Levo-T4. If solitary and large,view by US, then do I-131 uptake. Active uptake ["hot"] is OK, No uptake ["cold"] may be malignant -> biopsy

Four kinds of thyroid tumors

Papillary [75%, most female, rarely metastasize, Tx: resection]; Follicular [15%, women > 50, may metastasize to lung/bone, Tx: resection/I-131]; Medullary [5%, very aggressive, metastatic to liver, lung, bone; Tx: resection]; Anaplastic carcinomas [5%, very aggressive with poor prognosis, Tx: radiation/chemo]

Post-thyroidectomy Tx

Whole-body I-131 scan to destroy any metastasis, then High Dose RAI ablation; repeat in 1 yr. High-dose Levo-T4 for 5 yrs to ensure TSH is not present, in case of metastasis, then normal dose

Thyroid replacement drug that replaces endogenous T3

Liothyronine [Cytomel]; used in conjunction with Levothyroxine for pts with poor T4-> T3 conversion.

When thyroidectomy is done

Significant obstructive thyromegaly

Treatment for acute thyroiditis

Corticosteroids to reduce inflammation

Gold Standard for thyroid mass imaging

Ultrasound

Distinguishing cancerous thyroid nodules from benign

I-132 uptake scan:
"Hot" [I-131 uptake POS] are usually benign,
"Cold" [I-132 uptake NEG] are likely malignant-- biopsy!!

Only definitive Thyroid CA diagnostic procedure.

Biopsy [needle or tissue]

Relationship between thyroid CA & labs

None: Thyroid CA is not associated with T3/T4/TSH changes.

Adrenal cortex regions and hormones

Go Find Rex, Make Good Sex;
Granulosa [Mineralocorticoid-> aldosterone];
Folliculata [Glucocorticoid-> cortisol];
Reticularis [DHEA-> -> testosterone]

1st line Adrenal insufficiency Tx & SE

Adrenal insufficiency-> Addison's-> ADD cortisol!
Hydrocortisone = Cortef 25-30 mg total, divided BID; SE: Weight gain, HTN, Immuosuppression, DM

Two hormones with mild mineralocorticoid activity

Progesterone & Deoxycorticosterone

Cortisol effects

Increase BP, Increase [glu] by gluconeogenesis, Inhibit insulin, antidiuretic [water retention]

Cortisol diurnal cycle

Lowest 3 hrs into sleep;
Highest in early morning

Adrenal insufficiency name, S/s

Addison's; Fatigue, dizzy, weakness, weight loss, diarrhea, hypotension, hyperpigmentation

Adrenal Insufficiency Types

Primary: Adrenal dysfunction
Secondary: Ant pituitary fails to make ACTH
Tertiary: Hypothalamus fails to make CRH
Autoimmune (2/2 DM-1, Grave's Hashimoto's)

Addisonian Crisis occurence & S/s

In untreated Addison pt or Addison pt w/ Ix/fever (often meningococcal septicemia = WATERHOUSE FRIDERICHSON SYNDROME); V/D, Dehydration, Weakness, hTN, Hypoglycemia, Fever

2nd line adrenal insufficiency Tx

Predisone or prednisolone (prednisone metabolite). Has less mineralocorticoid activity then hydrocortisone

Mineralocorticoid replacement Rx

Fludrocortisone (usually used w/ hydrocortisone)

Adrenal Excess condition

Cushing's

Ranked causes of Cushing's

1. Iatrogenic (corticosteroids/steroids)
2. Secondary (pituitary mass/tumor)
3. Primary (adrenal adenoma)
4. Ectopic tumor (Small cell lung CA)

Cushing's Dx lab tests

Elevated cortisol in serum & 24-hr urine

Cushing's Dx

Dexamethasone suppression test is NEG:
1. ACTH: Absent/Low; CORTISOL: Not suppressed by high OR low doses; Dx: Primary 2. ACTH: Elevated; CORTISOL: NOT suppressed by LOW, but IS suppressed by HIGH; Dx: Secondary
3. ACTH:Normal to Elevated; CORTISOL: Not suppressed by high OR low doses; Dx: Men

Cushing's S/s

Central obesity, Moon face/buffalo hump, Hirsutism, Amenorrhea, Truncal striae, HTN, Acne

Cushing's Tx

Iatrogenic: discontinue meds;
Secondary: Resection of pituitary tumor
Primary: Resection of adrenal adenoma
Follow resections by hormone replacement until ACTH rises again

Neuroendocrine adenomas that release catecholamines

Phaeochromocytoma

Phaeo S/s

HTN, Tachy, Red flushing, Palpitations, Diaphoresis, Anxiety, HA

Phaeo Dx

Plasma free metanephrine (Epi metabolite) elevated (Gold standard), 24-hr urine metanephrines/catecholamines; MRI to localize
(May be MEN: parathyroid, pancreas, GI)

Phaeo Tx

Resection following PHENOBENZAMINE (prevents severe HTN in surgery)

Phaeo contraindicated Rx

Beta Blockers (don't block alpha sites, get rebound HTN)

Diabetes Insipidus types & etiology; Tx

1. ADH deficiency from POST pit ; Tx: vasopressin replacement (Desmopressin) given as nasal spray, OR
2. Inability to bind ADH at collecting ducts; Tx: Hydrochlorothiazide

Calcium regulating glands; MOA

Parathyroids; Resorb Ca2+ from bone, Retain Ca2+ at gut (via Vit D) and recover Ca2+ at kidney

Hypoparathyroidism S/s

Hypocalcemia-> Muscle cramps/tetany, Parasthesia, Dry hair/skin, QT elongation, Brittle nails, Seizure

Hypoparathyroidism Tx

Ca2+ & Vit D replacement, monitor regularly to avoid arrhythmia (short QT) and Stones, Bones, Moan, Groans

Hyperparathyroidism S/s

Hypercalcemia-> Stones, Bones, Moans, Groans, Thrones

Parathyroid Tumor test

Sestamibi PT scan using Tc-99m isotope (uptake is faster in hyperthyroidism)

PT tumor resection indications

Under 65, cut it out. Under: monitor
Can't find ectopic tumor but have elevated Ca? Take out largest PT gland.

How are the various types of Adrenal Insufficiency diagnosed?

ACTH Stimulation test: "Cosyntropin" is given, then cortisol levels checked.
If no (or v. slight) cortisol increase: PRIMARY Addison's;
If 2-10X increase: SECONDARY
**For AI Adrenal Insufficiency, 90% in US, measurement of 21-hydroxylase autoantibodies is done

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