Females: Triggers ovulation, Devt of corpus luteum;
Males: Production of testosterone by Leydig cells
Stimulates Adrenal cortex to release the cortical triad: Aldosterone, Cortisol, Androgens
Also called vasopressin, ADH promotes water reabsorption at the collecting ducts, & mediates vascular constriction
Description of pituitary masses
Most are benign but many secrete 1 or more hormones; 10% of all reported intracranial masses; ≤25% population
Most common pituitary adenomas, effect, gender distribution
Prolactinomas; cause hyperprolactinemia and gynecomastia; occur mostly in females
Symptoms of Hyperprolactinemia
Galactorrhea, Breast enlargement & tenderness, Anovulatory amenorrhea, dysmenorrhea, Decreased libido, ED
Bromcriptine [Parlodel]- a semisynthetic ergot; dopamine receptor agonist, or Cabergoline [Dostinex]- an ergot derivative used to treat Parkinson's, but associated with gambling compulsion.
Bromcriptine uses; Trade name; Mechanism; Contraindications
Dopamine agonist used in the treatment of pituitary tumors, Parkinson's, Hyperprolactinaemia, Neuroleptic Malignant Syndrome, and DM2. For Hyperprolactinemia, given as Parlodel. Mechanism: decreases Prolactin; Bromcriptin is contraindicated in breastfeeding
Do not use with Triptans, [serotonin receptor agonists used in migraine treatment]; Decongestants, where they may cause hypertension and tachycardia; and Antipsychotics, where hypertension may result
Cabergoline use; Trade name; Mechanism; Contraindications
Hyperprolactinemia treatment (Dostinex); dopamine agonist @ Anterior Pituitary.
Cabergoline decreases prolactin, and is contraindicated in breastfeeding.
Short Stature diagnosis
2 standard deviations below average for age/gender.
Gold standard is Insulin Tolerance Test. [0.1 microgram per Kg] insulin is followed by sampling for growth hormone. If GH > 5, [10 in kids], positive for GH deficiency
Short stature treatment. What are the interactions and side effects?
GH daily injection: Nutropin, Humatrope, Genotropin; Increases bood glucose, decreases INR in Coumadin patients. May cause diabetes, hypertension, and pancreatitis
Acromegaly diagnosis. What is the treatment, and what secondary pathologies occur if untreated?
GH levels are measured 1 hour after a 1 hour glucose tolerance test. If GH exceeds 1 microgram per liter, test is positive.
Treatment is surgical resection & Octreotide IM (Sandostatin) or Lanreotide IM (Somatuline);
Untreated, may cause cardiomegaly and CHF, hypertension, diabetes, renal failure, & visual disturbance from tumor
Thyroxine forms & distribution
T4: 90%, T3: 10%. T3 is four times stronger. 99% is bound to TBG, [Thyroid Binding Globulin]; only free hormone is active.
Thyroxine regulating gland & hormone; regulatory mechanism
The anterior pituitary regulates the thyroid via TSH [Thyrotropin], in response to T4 levels
Second Thyroid hormone & function
Calcitonin, a calcium ion regulator that opposes PTH. Calcitonin decreases serum calcium.
Hypothyroid signs and symptoms
Fatigue, Weight gain, Depression, Hair loss, Dry skin, Dysmenorrhea, Bradycardia
Hashimoto's; Gender distribution; Mechanism
Autoimmune hypothyroidism; 10 times more females; Thyroid peroxidase antibodies bind & inhibit T4; Insidious onset with hyPER-thyroid 1st; High genetic correlation
Non-pitting edema with severe hypothyroidism, Reduced cardiac output, mental slowing, hair loss. Myxedemic coma may be precipitated by stroke or MI
Hypothyroidism treatment & Allergic concern; What is an alternative?
Levothyroxine (LT4) (Synthroid or Levothroid); Made with lactose binder. In lactose intolerant patients,
dessicated thyroid [porcine or bovine] may be used.
Grave's disease; signs and symptoms
Autoimmune Hyperthyroidism (Agonist effect); Symptoms include nervousness, tachycardia, weight loss, exophthalmia, hyperhidrosis, tremor, insomnia
Grave's disease drug names & mechanism; What are some side effects?
Methimazole and Propylthiouracil, PTU. Both inhibit addition of iodine to thyroglobulin to block T4 synthesis; May cause Leukopenia, Agranulocytosis, Aplastic Anemia; Hepatotoxicity. PTU also alters INR in Warfarin treatment.
2nd line Grave's disease treatment
Ablation with I-131 or thyroidectomy, followed by thyroid replacement treatment, i.e., lifelong thyroxine.
Acute Thyroiditis diagnosis and treatment
Defined as "hyperthyroidism secondary to infection." Differentiated from Grave's by radioactive iodine uptake. Note: I-131 uptake by Grave's is high; uptake in Acute [=Toxic] Thyroiditis is low. Treatment is oral steroids [prednisolone].
How thyroid masses are evaluated
40 to 50% of all adults; Usually benign tumors, but rarely may be cysts. Ultrasound is diagnostic Gold Standard. Cysts usually resolve, but may be needle aspirated
Thyroid nodule diagnosis and treatment
If solitary & large, over 1.5 cm, view by ultrasound, then do I-131 uptake. Active uptake, termed "hot," is good; no uptake [cold] indicates mass may be malignant. Biopsy!
Four kinds of thyroid tumors
1) Papillary: 75%, most female, rarely metastasize. treatment: resection;
2) Follicular: 15%, women over 50 years, may metastasize to lung or bone. Treatment: resection and then "blast" with I-131)
3) Medullary: 5%, very aggressive and metastatic to liver, lung, and bone. Treatment: resection.
4) Anaplastic carcinomas 5%, very aggressive with poor prognosis. Treatment: radiation & chemo.
Three step process:
1) Whole body I-131 scan to identify residual thyroid tissue & any metastasis, then,
2) High dose "radioactive remnant ablation;" repeat in 1 year.
3) High dose Levothyroxine-T4 for 5 years to ensure TSH is not present, in case of metastasis, then normal dose levothyroxine for life.
Thyroid replacement drug that replaces endogenous T3
Liothyronine [Cytomel]; used in conjunction with a T4 drug, Levothyroxine, in patients with poor T4 to T3 conversion.
When thyroidectomy is done
When malignant nodules are identified or if significant obstructive thyromegaly occurs.
Distinguishing cancerous thyroid nodules from benign
I-132 uptake scan:
"Hot," in which I-131 uptake occurs, are usually benign,
"Cold," in which I-132 uptake is minimal, are likely malignant-- biopsy!!
Relationship between thyroid cancer & labs
None: Thyroid cancer is not associated with T3/T4/TSH changes.
Adrenal cortex regions & hormones
Go Find Rex, Make Good Sex;
Granulosa [Mineralocorticoid-> aldosterone];
Folliculata [Glucocorticoid-> cortisol];
Reticularis [DHEA-> -> testosterone]
1st line Adrenal insufficiency treatment and side effects
Adrenal insufficiency-> Addison's-> Add cortisol!
Hydrocortisone (= Cortef) 25-30 mg total, divided BID; Side effects: Weight gain, hypertension, immunosuppression, diabetes
Increase BP, Increase [glu] by gluconeogenesis, Inhibit insulin, antidiuretic (water retention)
Adrenal insufficiency name. What are the signs and symptoms?
Addison's; fatigue, dizziness, weakness, weight loss, diarrhea, hypotension, hyperpigmentation
Adrenal Insufficiency Types
Primary: Adrenal dysfunction
Secondary: Anterior pituitary fails to make ACTH
Tertiary: Hypothalamus fails to make CRH
Autoimmune: secondary to Type 1 diabetes, Grave's, and Hashimoto's
Addisonian Crisis occurence & signs and symptoms
In untreated Addison patient or Addison patient with infection and fever, often seen in meningococcal septicemia = Waterhouse Friederichson syndrome; vomiting and diarrhea, dehydration, weakness, extreme hypotension, hypoglycemia, fever
2nd line adrenal insufficiency treatment
Prednisone or prednisolone (prednisone metabolite). Has less mineralocorticoid activity then hydrocortisone
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]
Dexamethasone suppression test is NEG:
1. ACTH: Absent or Low; Cortisol: Not suppressed by low or high DMS doses; Diagnosis: Primary Cushing's
2. ACTH: Elevated; Cortisol: not suppressed by low DMS level, but is suppressed by high DMS; Diagnosis: Secondary Cushing's
3. ACTH: Normal to Elevated; Cortisol: Not suppressed by low or high DMS doses; Diagnosis: Ectopic tumor
Cushing's signs and symptoms
Central obesity, Moon face/buffalo hump, Hirsutism, Amenorrhea, Truncal striae, HTN, Acne
Iatrogenic: discontinue meds or steroids
Secondary: Resection of pituitary tumor
Primary: Resection of adrenal adenoma
Ectopic: Find and resect tumor
Follow resections by hormone replacement until ACTH rises again
Phaeo signs and symptoms
Hypertension, Tachycardia, Red flushing, Palpitations, Diaphoresis, Anxiety, Headache
Plasma free metanephrine [Epi metabolite] elevated. [Gold standard]= 24-hour urine metanephrines and catecholamines; MRI to localize
May be component of Multiple Endocrine Neoplasm-Type 2: Parathyroid hyperplasia, medullary Thyroid carcinoma, Phaeochromocytoma
Resection following phenobenzamine, a drug given to prevent severe hypertension in surgery.
Phaeo contraindicated drug. Know this!
Beta Blockers. Because they don't block alpha sites, patient gets rebound hypertension
Diabetes Insipidus types & etiology; treatments
1. Central diabetes insipidus: ADH deficiency from posterior pituitary ; Treatment: vasopressin replacement [Desmopressin] given as nasal spray,
2. Nephrogenic diabetes insipidus: Inability to bind ADH at collecting ducts; Treatment: Hydrochlorothiazide antidiuretic.
Calcium regulating glands; MOA
Parathyroid glands; Resorb calcium ions from bone, Retain calcium ions at gut via Vitamin D; and recover calcium ions at kidney
Hypoparathyroidism signs and symptoms
Hypocalcemia-> Muscle cramps/tetany, Parasthesia, Dry hair/skin, QT elongation, Brittle nails, Seizure
Calcium & Vitamin D replacement, monitor regularly to avoid arrhythmia [short QT!] and Stones, Bones, Moan, Groans
Parathyroid Tumor test
Sestamibi parathyroid scan using Tc-99m isotope. Uptake is faster in hyperthyroidism.
Parathyroid tumor resection indications
Under 65, cut it out. Over 65: monitor
Can't find ectopic tumor but have elevated Calcium? Take out largest parathyroid gland.
How are the various types of Adrenal Insufficiency diagnosed?
ACTH Stimulation test: "Cosyntropin," a synthetic ACTH, is given. Then cortisol levels are checked.
1) If no or very slight cortisol increase: PRIMARY Addison's;
2) If 2 to 10 times increase: SECONDARY Addison's
**For Autoimmune Adrenal Insufficiency, [90% of U.S. cases], measurement of 21-hydroxylase autoantibodies is done.