1- Introduction to endo, Diseases of the hypothalamus

What is a hormone

Signalling molecule that travels from its site of production to far sites and exert action

What are the major forms of hormones

• simple- AA derivatives

  • thyroid hormones, adrenal catecholamines

• steroids- adrenal cortex, gonads

• peptides- eg TRH

• complex proteins- eg pituitary hormones

What are the processes regulated by hormones

• maintenance of homeostasis

• adaptation to internal and external circumstances

• regulation of metabolism

• growth and development

• other physiological processes

  • heart + bowel function, BP etc

Describe the receptors they act on

• Protein hormones- membrane receptors

• Steroid hormones- intracellular receptors

What is the hypothalmic-pituitary system

• Hypothalamic nuclei make + release hromones

• Stotred in posterior lobe of pituitary

• Released through small cell tuberoinfundibular neurosecretory system

What are the hormoens produced by the hypothalamic- pituitary system

• Hypothalamus

  • CRH, TRH, GnRH, GHRH

• Pituitary

  • Posterior- neurohypophysis

    • ADH

    • Oxytocin

  • Anterior- adenohypophysis

    • ACTH, TSH, LH, FSH, GH, prolactin

What is the role of prolactin

• stimulation of milk production in women

• inhibits LH/ FSH secretion from pituitary

• other, clinically minor effects- immunological, stress effects

• Only pituitary hormone that is INhibited by hypothalamus- hypothalamic dopamine

What is the role of growth hormone

Direct effects and via IGF 1 secreteion- cell proliferation and growth promotion, increases blood glucose levels

What is the role of ADH

Increasing water resorption from kidney collecting channels via the AVP2 receptor

Most potent vasocosntrictor via AVP1 receptor

What is the role of oxytocin

• Uterus contraction, lactation

• no disease related to its overproduction

What are the thyroid hormones

• T3 active, T4 inactive

• T4-3 conversion happens in peripheral organs

  • regulated by deiodinase enzymes

  • = Selenoproteins

• T4 made in larger quantities

• T4 stored in colloid bound by thyroglobulin

• calcitonin

What is the role of thyroid hormones

• development of CNS, heart

• major regulator of metabolic functions

• overproduction- weight loss, tachycardia, increased bowerl movements, subfebrile, hyperactivity

What is calcitonin

• produced by thyroid C cells

• in regulation of Ca metabolism- reduces blood calcium levels

Describe the parathyroid gland

• 4 behind thyroid

• functioning is not regulated by hypothalamus

• secretion is regulated by calcium sensors in parathyroid cells membrane

What is the role of parathyroid hormones

• stimulates osteoclast activity → increased calcium release, 1 alpha hydroxylation of Vit D, calcium resorption from kidney

• increases blood caclium levels

• vit D- stimulates calcium resorption from intestines, calcium deposition in bone

Describe the glucocorticoids

• Cortisol

• main regulator of metabolism

• increases glucose formation + release → increase blood glucose levels

• stimulates protein + fat degradation- catabolic hormone

• Inhibits bone formation, stimulates bonr degradation

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Describe the sex hormones

• Pulsatile secretion

• negative feedback- inhibin secreted by gonads

• activin- positive autoregulatory loop

What are the types of amenorrhea

Primary

Secondary

Define amenorrhea

• primary- no menstrual cycles till the age of 16

• Secondary- formerly, but doesn’t occur any more, if regular for min 3months, if irregular menses for 6 months

What are the examples of physiological secondary amenorrhea

• pregnancy

• menopause

Define oligomenorrhea

• infrequent menstrual cycles

Define galactorrhea

Lactation in non suckling women

Define hirsutism

Increased body hair in androgen dependent skin regions

Define hypertrichosis

Increase hair in non androgen dependent regions

Forearm, lower leg

Define primary insufficiency

• Disease of the peripheral hormone producing organ

• peripherial hormone low

• pituitary hormone increased

Define secondary insufficiency

• Lack of pituitary front lobe hormones

• at the level of pituitary

• Peripherial + pituitary hormone low

Define terriary insufficiency

• Lack of hypothalamic trophormones

• At the level of hypothalamus

• All hormone levels are low

What are the main forms of hormone diseases

• hormone deficiency

• disturbance of hormone action

• hormone overproduction

• endocrine tumour without hormone overproduction- hormonally inactive

What are the causes of hormone deficiencies

• developmental disorder of endocrine glands

• autoimmune damage

• lack of substance needed for hormone formation

What are the causes of disturbances of hormone action

• receptor dysfunction

• hormone resistance syndromes

What are the causes of hormone overproduction

• hormone producing tumours

• hormone overproduction due to autoimmune disease

  • eg Graves

What are the types of neuroendocrine tumours

• tumours of neuroendocrine organs

• tumours originating from dispersed neuroendocrine cells

  • carcinoid tumours

What are the tumours of neuroendocrine organs

• Pituitary- PitNET

• adrenal medulla- pheochromocytoma

• parathyroid gland

• thyroid C cells- medullary thyroid cancer

What are the tumours originating from dispersed neuroendocrine cells

• mostly GI

• of respiratory tract

What are the classifications of neuroendocrine neoplasia

• Well differentiated NET

  • NEN Grade 1- Ki 67 <3%

  • NEN Grade 2- Ki67 3-20%

  • NEN Grade 3- Ki67 >20%

• Neuroendocrine carcinoma

  • NEC G3- poorly differentiated- small or large cells- Ki67 >20%

• Mixed adenoneuroendocrine carcinoma- MANEC

  • or MINEN- mixed neuroendocrine non neuroendocrine neoplasm

• Hyperplastic or preneoplastic lesions

Define paraneoplastic syndrome

Syndrome that is not due to size, invasion or metastasis of tumour,

Due to soluble mediator secreted or an immune reaction induced by tumour that can have effects indistant areas

What are the characteristics of paraneoplastic syndromes

• in ~8% of all malignant tumours

• very rare in benign

• endocrine, hematological, neurologic, dermatologic paraneoplasis etc

• variable clinical pictures → can lead to tumour diagnosis

What are the causes of hypothalamic dysfunction

• tumours

  • astrocytoma, glioma, germinoma, craniopharyngeoma, big pituitary tumours, lymphoma

• bleedings

• developmental abnormalities-

  • arachnoid cysts, holoprosencephaly

• granulomatous inflammation

  • histiocytosis X, sarcoidosis, TBC

• Inflammation- encephalitis, meningitis

• trauma

• irradiation

• inherited diseases

What are the diseases of the hypothalamus

• Lack of trophic hormones

• deficiency of posterior pituitary hormones

What are the consequences of a lack of trophic hormones

• growth delay

• hypopituitarism

• disorders of sexual development

  • isolated GnRH deficiency- Kallmann syndrome

What are the consequences of posterior pituitary hormones

Diabetes insipidus

What are the non endocrine consequences of hypothalamic disorders

• Appetite problems

  • anorexia, hyperphagy, obesity

• disorders of liquid homeostasis

  • adipsia, polydipsia

• disorders of thermal regulation- hyperthermia, hypothermia

• somnolence, coma

• mood problems