Endo E2 -MEN & Disorders of testes

What are features of hypogonadism?

diminished libido/erections, fatigue, depression, reduced exercise endurance, dec growth of body hair, testes small or normal, low serum total testosterone or free testosterone

Serum LH & FSH are low or normal:

Hypogonadotropic hypogonadism

Serum LH & FSH are high:

Hypergonadotropic hypogonadism (testicular failure)

What causes Hypogonadotropic hypogonadism?

Insufficient gonadotropin secretion by pituitary gland

What causes Hypergonadotropic hypogonadism?

Pathology in the testes themselves

What are some causes of hypogonadotropic hypogonadism?

aging, alcohol, congenital syndromes, hemochromatosis, hypopituitarism, kidney disease

What are some drugs that can cause hypogonadotropic hypogonadism?

estrogen, GnRH agonist, ketoconazole, prior androgens, spironolactone

What are some causes of Hypergonadotropic hypogonadism?

aging, AI, Klinefelter syndrome, Lymphoma, orchitis, testicular trauma, Tb

LH --> ________ --> Testosterone

Leydig cells

FSH --> ________ --> Inhibin

Sertoli cells

Where does testosterone have negative feedback?

Anterior pituitary and hypothalamus

Where does inhibin have negative feedback to?

Anterior pituitary only

What is primary hypogonadotropic hypogonadism?

failure to enter puberty by age 14, with causes including isolated hypogonadotropic hypogonadism, hypopituitarism, or simple constitutional delay of growth and puberty

What are some genetic conditions that can cause acquired hypogonadotropic hypogonadism?

Kallmann syndrome, X-linked congenital adgrenal hypoplasia, Prader-Willis syndrome

What is partial hypogonadotropic hypogonadism (age-related hypogonadism)?

Serum testosterone in range of 150-300 ng/dL along with obesity, poor health, or normal aging

What is preserved in age-related hypogonadism?

Spermatogenesis

What is the MC chromosomal abnormality in males?

Klinefelter syndrome (47,XXY)

*testes appear normal during childhood, but become firm, fibrotic, small, and nontender during adolescence

Men with acquired hypogonadism have manifestations, known as "testosterone deficiency syndrome"- what sx are included in this?

ED, poor morning erection, or hot sweats

When does dec hair (body, axillary, beard, or pubic) occur in hypogonadism?

only after years of severe hypogonadism

What is considered LOW serum testosterone?

< 320 ng/dL

What is considered LOW free testosterone?

< 64 pg/mL

If hypogonadotropic hypogonadism is suspected, what other hormone level (besides testosterone) should be looked at?

Serum prolactin

What is the tx for hypogonadism for boys who have not entered puberty by age 14?

Testosterone

In males with hypogonadism, trial of testosterone therapy may be considered if they have 3/6 symptoms- what are the 6 symptoms?

ED, poor morning erection, low libido, depression, fatigue, inability to perform vigorous activity

What are some contraindications of testosterone therapy?

Active breast or prostate cancer, untreated sleep apnea, heart failure

Where do tumors most commonly develop in patients with MEN 1?

Parathyroid glands

(next MC: endocrine, pancreas, duodenum)

What is Wermer's syndrome?

MEN1

In which MEN are cutaneous tumors common?

MEN1

*common on face/around nose

What types of cutaneous tumors may be seen in MEN1?

Angiofibromas, Collagenomas, Lipomas

Aside from skin lesions, what is often the 1st clinical presentation in MEN1 patients?

Hyperparathyroidism

*often by age 40

Which MEN may be associated with Zollinger-Ellison syndrome?

MEN1

*enteropancreatic tumors common

What might hyperprolactinemia cause?

amenorrhea

What might hyperparathyroidism cause?

hypercalcemia and recurrent nephrolithiasis

What are complications of MEN1?

nephrocalcinosis, osteoporosis, ZE syndrome

What is the tx for MEN1?

surgery to remove the tumor

Which MEN syndromes have a strong genetic component?

MEN1 & MEN3 (2B)

What is Sipple's Syndrome?

MEN 2A

What tumors are associated in MEN 2A?

Medullary thyroid carcinoma & pheochromocytoma

What MEN syndrome may be associated with Hirschsprung disease?

MEN 2A

Which makes up the majority of type 2 MEN?

MEN 2A

How should MEN 2 be diagnosed?

RET mutation testing before age 5 (dt being highly penetrant)

If mutation tests are positive in MEN2 what further action is recommended?

prophylactic thyroidectomy w/ lymph node dissection

Which MEN is associated w/ marfanoid habitus?

MEN 3 (2B)

What differentiates MEN 2A and MEN 3 (2B)?

MEN 3 has associated mucosal neuromas, ganglioneuromas, or marfanoid habitus

Which MEN is an autosomal dominant tumor caused by mutation in gene CDKN1B?

MEN4

What tumors are seen in MEN 4?

adenomas of pituitary, parathyroid glands, neuroendocrine tumors of pancreas

What is the key difference between MEN 1 and MEN 4?

Men 4 pts have NO mutation in menin gene

Which MEN is prone to adrenal tumors, renal tumors, testicular cancer, & neuroendocrine cervical carcinoma?

MEN 4

Which MEN syndrome is important to check 24-hour urinary catecholamines? Why?

Types 2A & 3 (2B)- bc of pheochromocytomas

Parathyroid involvement indicates which types of MEN?

MEN1 & MEN4

Facial angiofibromas indicate which type of MEN?

MEN1

Medullary thyroid carcinoma indicates which types of MEN?

MEN 2A & MEN 3

Interstitial ganglioneuroma indicates which type of MEN?

MEN 2B (3)