endocrine and kidney diseases - frara

Hypercortisolism

• The most common cause of hypercortisolism is exogenous, particularly due to drugs
• Endogenous causes include disorders of the pituitary gland
• Cushing was the first to perform transsphenoidal surgery to remove pituitary adenomas
  • This approach was a significant change because previous approaches were transcranial, requiring brain removal and causing extensive damage
• Every condition of endogenous hypercortisolism is considered Cushing syndrome
• Cushing first described ACTH-secreting pituitary adenoma and related clinical features

Hypothalamus-Pituitary-Adrenal Axis

• CRH stimulates ACTH secretion, subsequently stimulating cortisol secretion.
• Negative feedback suppresses ACTH and CRH secretion
• Pituitary gland diseases can cause high or normal ACTH levels
• Adrenal gland problems cause very low ACTH levels due to suppression

ACTH Levels

• ACTH levels below 5 pg/mL are associated with adrenal hypercortisolism, considered ACTH independent
• ACTH levels of 5–10 pg/mL are considered a "gray zone," not indicating pituitary or adrenal association
• ACTH levels above 10 pg/mL indicate ACTH-dependent hypercortisolism

ACTH Dependence vs Pituitary Association

• ACTH dependence is better than pituitary association, as the latter accounts for only 80% of ACTH-dependent cases
• Other causes include pituitary hyperplasia (1-2%), ectopic ACTH, or ectopic CRH secretion
• Neuroendocrine tumors may secrete various hormones, affecting the hypercortisolism clinical picture
• Ectopic ACTH-dependent hypercortisolism typically involves lung or bronchial carcinoid
• Patients with small cell lung cancer frequently have concomitant ACTH secretion
• No differential diagnosis can be made based on biochemical evaluation at baseline
• No biochemical difference exists between ACTH produced by the pituitary gland and ectopic forms

Cushing's Syndrome

• Adrenal disorders account for less than 20% of Cushing's syndrome
• The most frequent cause is adrenal adenoma, with carcinoma being rare
• Adenomas and carcinomas can be distinguished by adrenal androgen secretion, which is high in adrenal carcinoma
• Genetic diseases like pigmented and macronodular hyperplasia can cause endogenous hypercortisolism
• Carney Complex (CNC) is an autosomal dominant disorder with hypercortisolism due to bilateral pigmented adrenal nodules and other tumors

Clinical Manifestations of Cushing's Disease

• Patients with hypercortisolism are prone to infections due to immune system suppression
• Effects on connective tissue cause striae rubrae on the abdomen, lads, and armpits
  • These red/purple stripes are large compared to pregnancy skin lesions, indicating vessel involvement
• Hypercortisolism stimulates osteoclastic function and inhibits osteoblasts, leading to osteoporosis
  • Negative calcium balance, low intestinal absorption, and increased kidney discretion also factor
• Systemic effects on the CNS include depression and ocular hypertension leading to glaucoma
• Endocrine system effects include functional GH deficiency and hypogonadotropic hypogonadism
• Metabolic effects induce insulin resistance, hyperglycemia, and diabetes
• Hypertension relates to catecholamine secretion and sensitivity and their positive ionotropic effect
• Specific signs include easy bruising, full moon facies, and myopathies with striae
• Cushing syndrome patients do not typically present with hyperpigmentation
• Hyperpigmentation is typical in adrenal insufficiency where ACTH levels go from 100 to 1000
• In pituitary adenomas or ectopic forms, ACTH levels are usually between 100-200
• A patient with MEN1 (multiple endocrine neoplasia type 1) and a small pituitary adenoma may have striae rubrae and hypercortisolism
• Hypercortisolism is confirmed with 24h urine free cortisol evaluation and the Nugent test
  • Nugent test means overnight 1 mg dexamethasone suppression
• Basal ACTH levels can be normal, so hypercortisolism diagnosis cannot be based only on ACTH levels
  • Assess ACTH dependence or independence instead
• Hirsutism can be present and is another sign of Cushing, indicates adrenal carcinoma because adrenal glands produce androgens
• Proximal muscle wasting is another manifestation of hypercortisolism due to changes in body composition Patients typically have increased abdominal size
• Plethora and gynecomastia can be seen, are frequent in males because of hypogonadism, but in patients with a macroadenoma it is associated with hyperprolactinemia
• Cushing needs to be excluded in patients with gynecomastia
• Buffalo hump is also an indication
• In children, Cushing presents with buffalo hump and obesity with wasting muscles
• Cushing is detected based on how children fail to maintain percentile
  • Height decreases
• GH deficiency needs to be excluded and solving disease associated to GH deficiency can restore the final height of the patient

Diagnosis of Hypercortisolism

• Three screening tests exist and the first step is excluding exogenous glucocorticoid exposure
  • Most common drug is prednisone, including oral pills, inhalatory forms, and injections
• Three tests for screening:
  • 24h urinary free cortisol evaluation
  • Nugent’s test (overnight 1mg dexamethasone suppression): Serum cortisol level above 18 ng/mL or 1.8 pg/dL is positive
    • Some guidelines use 5 μg/dL as diagnostic but 18 ng/mL is best
  • Late-night salivary cortisol: Useful because cortisol rhythm is lost in Cushing's patients
    • Patient puts a sponge in the mouth before washing teeth, puts it in the fridge, and gives it to the lab
• Some tests cannot be used for specific populations
  • Patients with chronic kidney disease cannot use the 24h urinary free cortisol test
    • Low-dose dexamethasone test should be performed
  • Nugent test has higher sensitivity and specificity in patients with adrenal incidentaloma

Further Diagnostic Steps

• Exclude physiological causes of hypercortisolism or related diseases like uncontrolled diabetes, alcoholism, pregnancy, or depression
• Obesity affects test results, so perform the Liddle test, a high-dose dexamethasone two-day suppression test
  • Patient takes dexamethasone every 6 hours for 2 days, checking serum cortisol
  • The Liddle test is the same as the Nugent test, but the dose and duration are higher, yet the diagnostic threshold is the same
• Liddle test helps determine ACTH levels.
  • ACTH below 5 pg/mL: ACTH-independent
  • ACTH normal or above 10 pg/mL: ACTH-dependent
• ACTH evaluation requires proper handling of the refrigerated blood sample to avoid destruction
  • In ACTH-dependent hypercortisolism, diagnose pituitary adenoma or ectopic ACTH secretion via MRI, deviation of the pituary stalk
    • Have hyperprolactinemia IPSS test is then performed if something is not found or tumor is small
  • Use IPSS test by Inferior petrosal -Check blood -Expect higher levels of ACTH compared -Check bilatery ACTH compared at petrosal venous sampling CRH needs to be administered for IPSS
  • Pituitary maintains response, adenoma should start secreting more ACTH -No response if ectopic or neuroendocrine in abdomen For ACTH need to check adrenal glands
  • Adrenal adenoma are present bilatery or lesions

Therapy for Hypercortisolism

• First line remains surgery removing neoplasms associated with the ACTH production
• Explore surgery but unsuccessful
• Can use - Medical therapy by inhibiting ACTH secretion through domaine agonists like cabergoine or Somatostatin
  • Use enzymes using steroidigeniss
  • Mitotane is usually used in adrenals or carcnoma by inhibiting coristal and tumors shrinking
  • Use mfiprestone used from for aborting
• Can not be manager because cortisol not administer from corticoseroids Final is adrenaletomy
• ACTH depends the desiesa
• remove only grand respond of ACTH
• causes insufficnety
• raditation preformed due to developed need for a strong need
• shouldnt work because drugs must work instead

Male Hypogonadism

• Infertility and male hypogonadism are frequent
• The prevalence is high at 1 in 10 in males
• Sexual differentiion starts at 6th week of mbryonic develpment on y and has a speicifi region coodfy
• without haveing it it becomes testostone insenstive that is caled Morris syndrome where there are high levels , people affeceted affected have male and male karoytoype
• diagmosed during puberty for abscence and testictiles will need to be takne out and given estrgoems

Questios

• wont be getting meneses, she remans unfertille need sec hormone store
• breast from estogen receports in body
• can have Labibia and vaginas
• completly insensitve and needs repaltions like estorgen
• testiciles needs be remvoed

The hypothalamus-pituitary-gonadal axis

• The Gnrh will stimulated the secrete 60 to 90 min and FH an dLH FSH STIMUALTE SPERMATOGEOnia
• The tail will in acid enviiremt
• head contains chromosomes

Testosterone

Leydigcells produce cholesterol to synthezie

• free 2 under 2 %, testostone under circatoulion

• androgyn recpeotr wirth cels

• hair Growth

• embryo differiation

• deepen voice

• musculation

• sperm produticion

• exggenous administration with infetility

• replacement of estergem is hygher and repress lh dh

• stop sperm duction

regulation of sex

• erectile distfucntion
• testo does prodfuection affect
• morning erectios affect
• peak producititon is after birthm
• elderl level is low

diseases

• prescositour puberty
• abnormbal early ond set
• enalrenent y younger then 10
• independent condittions
• eterpic androgen cancer
• tumor is condiftions

GnRhh ANALOUS INHIMBIT GNRH FSH SECERATION with a PUUSATILE RYTHYM Puberty late at 16 years old needs exclsuive testies

• TESTIIS IN SHROUTM SO INFLUENCE CANCER
• EARLY DIAGNOUSC IS CANCER
• if surgy is formred early life expectancy be creased and reoccur

prE AND POST PYbERTAL

testoserein impair and prodection or spermogensis befroe puberty - small scritum Hypogandiim

• 4m or 15 mnle

Testies reach stage 3 the testicle

• have high levels and
• can be a postivie effeCt If dont wutrhdwon you get inferiille Lh and Lih and FSH are low children without anndrogen Testosternie will creased the puberty with test

Is it poisblle extra?

Is is in patients

• teststerone Beard Prilmay

• Acuisir form Testicie and variclous is highy If kanflighter synridm thendegrenrtion

• synfdorems high and need to replate Tesyis and cancer gynecomnsta

• high androrgen Kandafller sybdorem

Secondary hyp

hypogandoitric hypohandim all aquie4ddesies

• kadmander syndroeme d
• anoshia

Diaagonsi

• under 2m.1 if 8 its daihndist
• 2,3 is gray zone

measure FREE

• define from Lh fh an dthe hypogandam

• sperm exam

• 1 to 5

• low sperm in volume

• count what they move

• if cant reach vo

• azrospermeris