Pathophysiology of endocrine system

Faculty of General Medicine, Department of Pathophysiology, YSMU, 2020

 Types of humoral regulation

Characteristics Examples
Endocrine Hormone is released to the blood Thyroid hormones,
(distant) and binds to the target cells cortisol, sex hormones,
receptors. growth hormone.

Paracrine The signaling molecule acts on Somatostatin produced by

(interstitial) neighbor cells. pancreatic islet D-cells
influences on release of
insulin and glucagon.

Autocrine The signaling molecule acts on the Insulin regulates it’s own
same cell where it is produced. synthesis.

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 Hormone-producing organs and cells

Endocrine cells of organs and

Endocrine glands
tissues
GIT
Epiphysis
Heart
Pituitary Liver
Lungs
Thyroid gland Thymus
Kidneys
Pancreas
Adrenal glands
Testicles
Ovaries
Parathyroid glands
Hypothalamus
Adipose tissue BBB? 4
 The main functions of endocrine organs

Function Examples
1. Maintenance of homeostasis, Insulin, glucagon,
regulation of energy production, cortisol, growth hormone,
utilization and maintenance of aldosterone, etc.
normal functional terms
Growth hormone, sex
2. Growth and development hormones

3. Reproduction Sex hormones

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The two types of hormone-receptor interactions
Surface receptors have:
- Glucagon
- Insulin
- Epinephrine
- Parathyroid hormone
- TSH, ACTH, FSH, LH
- Antidiuretic hormone

Intercellular receptors have:

- Estrogens
- Testosterone
- Progesterone
- Adrenal cortical hormones
- Thyroid hormones (TH)

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A
ա B
Cortisol, ng/ml

light

Prasai M J et al. JCEM 2011;96:913-922 7

 Classification of endocrine disorders

Hyperfunction Hypofunction

Monoglandular Polyglandular

Partial Total
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 Major pathogenetic initiating units of
endocrine disorders
CNS
I. Impairments of
central regulation
Adenohypophysis

Endocrine gland II. Primary (proper)

glandular
Target cell

III. Extraglandular
Removal of hormones from the organism, e.g. or peripheral
by liver and kidneys

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 Causes of impairment of central regulation
Developmental defects and organic damages:
Cerebral hemorrhage, tumors
cortex Impairments of mental functioning:
psychosis, neurosis, prolonged stress reactions

Poisons (ethanol, narcotics) and infections

Genetic defects: mutations of genes for liberins and

statins, tropic hormones
Hypothalamus and
hypophysis
Direct damage: inflammatory processes, vascular and
traumatic damages, tumors

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 Impairments of hypothalamic
functioning
Impaired
transpituitary
regulation
- Thyroid gland (T3, T4) by TSH
- Sexual glands (sex hormones) by GSH
- Adrenal cortex (cortisol) by ACTH
- Liver (IGF-1) / somatomedin
Impaired
parapituitary
regulation
- Adrenal medulla (catecholamines)
- Pancreatic Langerhans islets
(insulin, glucagon, somatostatin)
- Parathyroid glands
(parathyroid hormone)
Parafollicular cells of thyroids (TCT)
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 +

TSH +/-
ACTH

FSH - ADH
Oxytocin
LH STH
prolactin

Anterior lobe 12
 CENTRAL REGULATORY MECHANISMS
Example of
Parapituitary Transpituitary Transpituitary

ANS

Tropic
hormone

ANS-autonomic nervous system

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 Relation between tropic hormone and target hormone

1.Insufficiency of target gland 2.Autonomic production

High
(primary hypothyroidism) of tropic hormone
(TSH-producing
adenoma)
Normal normal
3. Insufficiency
Tropic hormone (TSH)

of tropic hormone
(secondary
hypothyroidism) 4. Autonomic production of target hormone
(primary hyperthyroidism)
Low

Low Normal High

Target hormone(T4)
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 Impairment of hormone-target relationship

High
1.Secondary 2.Primary
Parathyroid hormone (pg/ml)

hyperparathyroidism hyperparathyroidism
60

Normal Norm

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4. Parathyroid hormone
3. Hypoparathyroidism non related
Low hypercalcemia

Low 85 Normal 105 High

Calcium (mg/l) 17
 Changes of exogenous and endogenous surrounding

CNS
-
Short feedback Long feedback

-
loop loop

Hypothalamus
Releasing
hormone

-
(e.g., CRH)
Tropic hormone (e.g.
ACTH) Anterior
pituitary gland

+ Peripheral gland (e.g., adrenal Hormone of peripheral

gland (e.g., cortisol)
cortex)
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 Manifestations of pituitary tumors

1. Hyperpituitarism
2. Hypopituitarism
3. Local signs, e.g. bitemporal hemianopsy 20
 Eosinophilic adenoma of
pituitary gland:
overproduction of growth
hormone

Acromegaly and gigantism

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 Metabolic effects of Oxitocin

Endocr Rev, Volume 41, Issue 2, April 2020, Pages 121–145, https://doi.org/10.1210/endrev/bnz012
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 Cushing syndrome

The arrow shows adenoma of adrenal The patient has “moon face”, central obesity, purple
cortex which produces cortisol. striae on the abdominal surface.

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 Multiple endocrine neoplasia

1. Type I (MEN-1) or Vermer syndrome, The

genetical basis – mutation of MEN1 gene suppressor
– pituitry, parathyroids, pancreas cancerogenic
transformation.
2. Type IIA (MEN-2A) or Sipple syndrome:
pheochromocytoma, medullary carcinoma,
parathyroid hyperplasia.

3. Type IIB (MEN-2B): pheochromocytoma,

medullary carcinoma, neuroma.
The genetic basis for MEN-2 is the RET mutation of
protooncogene. 24
 Iodine deficiency
Iodine is necessary for the production of T3 and T4

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 Which hormones
require transporters?

1. Peptide hormones are water soluble, hence they don’t require

transporters, Their “life span” is short,

2. Steroids are not water soluble, hence they are transported by their
corresponding transporter proteins, they stay in the circulation
relatively longer.
3. Thyroid hormones, despite they are derivatives of amino acid and
they don’t have “problem with solubility”, have specific transporters:
about 99.96% circulate in bound form. 26
 Laron syndrome (Laron
type dwarfism): genetic
defect of growth hormone
receptor

Zvi Laron, the Israeli researcher,

endocrinologist, who described the
syndrome in 1966.

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 Two “scenarios” of autoimmune damage of thyroid gland

A B

A. Hashimoto’s thyroiditis: lysis of thyroid gland B. Graves’ disease: stimulation of TSH receptors by
cells by autoantibodies and cytotoxic T autoantibodies resulting in hyperfunction. (LATS)
lymphocytes resulting in hypofunction.
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 Clinical Manifestations of Graves’ Disease.

Smith TJ, Hegedüs L. N Engl J Med 2016;375:1552-1565.

 Pathogenesis of
Graves’ Disease
Affecting the Thyroid
Gland and Orbit.

Smith TJ, Hegedüs L. N Engl J Med 2016;375:1552-1565.