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Three functions of Prolactin

Breast development; Milk production; Sexual gratification

LH functions

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

FSH functions

Females: Follicle growth and oogenesis;
Males: Spermatogenesis

ACTH function

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

GH [STH] functions

Stimulates growth, mitosis, & protein synthesis at bones & muscles

IGF-1 origin & function

Made at liver. Mediates, and is agonist for, GH

Four Oxytocin functions

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

ADH functions

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

Microadenoma versus macroadenoma

≤1cm X ≥1cm

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

Hyperprolactinemia treatment

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

Bromcriptine interactions

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.

Element required for thyroxine

Iodine

Cells producing T4 & mechanism

Follicular cells; bind Iodine to Thyroglobulin [TG]

Iodine-capturing enzyme

Thyroid Peroxidase, [TPO]

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

Hypo-iodinemia incidence

9% omnivores, 25% vegetarians, 80% vegans are low in iodine

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

Hashimoto's Labs

Thyroid peroxidase antibodies & TSH are elevated, T3 & T4 are depressed

Myxedema S/s

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.

Thyroid Replacement Monitoring

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

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.

1st line Grave's disease treatment

Methimazole (Tapazole), Propylthiouracil (PTU)

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.

Post-thyroidectomy treatment

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.

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," in which I-131 uptake occurs, are usually benign,
"Cold," in which I-132 uptake is minimal, are likely malignant-- biopsy!!

Only definitive Thyroid cancer diagnosis

Biopsy. Usually "fine needle," may be tissue.

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

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. 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

Mineralocorticoid replacement drug

Fludrocortisone. Usually used with 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-hour urine

Cushing's diagnosis

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

Cushing's treatment

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

Neuroendocrine adenomas that release catecholamines

Phaeochromocytoma

Phaeo signs and symptoms

Hypertension, Tachycardia, Red flushing, Palpitations, Diaphoresis, Anxiety, Headache

Phaeo diagnosis

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

Phaeo treatment

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

Hypoparathyroidism treatment

Calcium & Vitamin D replacement, monitor regularly to avoid arrhythmia [short QT!] and Stones, Bones, Moan, Groans

Hyperparathyroidism signs and symptoms

Hypercalcemia pentad: Stones, Bones, Moans, Groans, Thrones

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.

What are the components of Multiple Endocrine Neoplasia Type 1? Of Type 2?

Type 1: Hyperparathyroidism, Pituitary tumors [prolactinomas], and Pancreatic tumors [insulinoma or gastrinoma]
Type 2: Hyperthyroidism, Medullary thyroid carcinoma, and Phaeochromocytoma

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