Semmelweis University
First Department of Medicine
Dr. Szathmári Miklós
01. February 2010.
Scope of endocrinology 1.
• Growth
– Multiple hormones and nutritional factors
mediate the complex phenomenon of growth
• Short stature may be caused by GH deficinecy,
hypothyroidism, Cushing’s syndrome, precocious
puberty, malnutriton, and genetic abnormalities
• GH, IGF-1, thyroid hormones stimulate growth
• Sex steroids lead to epiphyseal closure
Functions of hormones 2.
• Maintenance of homeostasis
– Thyroid hormones control about 25% of basal
metabolism in different tissues
– Cortisol exerts a permissive action for many
hormones in addition to its own direct effects
– Parathormone regulates calcium and phosphorus
levels
– Vasopressin regulates serum osmolality by controlling
renal free water clearance
– Mineralocorticoids control vascular volume and serum
electrolyte concentrations
– Insulin maintains euglycemia in the fed and fasted
states
Integrated hormone action against
hypoglycemia
Rapid stimulation of
To antagonize insulin action
gluconeogenesis and glycogenolysis
Functions of hormones 3.
• Reproduction
– Sex determination during fetal development
– Sexual maturation during puberty
– Conception, pregnancy, lactation
– Cessation of reproductive capability at
menopause
Each of these stages involves an orchestrated
interplay of multiple hormones
Regulatory systems of hormone
production 1.
• Feedback control: both negative and positive, is
fundamental feature of endocrine system.
– Each of the major hypothalamic-pitutary-hormone axes is
governed by negative feedback:
• Thyroid hormones on the TRH-TSH axis
• Cortisol on the CRH-ACTH axis
• Gonadal steroids on the GnRH-LH/FSH axis
• IGF-1 on the GHRH-GH axis
– Feedback regulation also occurs for endocrine systems that do
not involve the pituitary gland:
• Calcium inhibits PTH secretion
• Glucose inhibition of insulin secretion
– Positive feedback control:
• Estrogen mediated stimulation of mid-cycle LH-surge
Regulatory systems of hormone
production 2.
• Local regulatory systems, often involving
growth factors:
– Paracrine regulation (factors released by one cell
that act on an adjacent cell in the same tissue:
somatostatin secretion of pancreatic δ-cells inhibits
insulin secretion from nearby β-cells
– Autocrine regulation (the action of a factor on the
same cell from which it is produced): IGF-1 acts on
many cells that produce it (gonadal cells etc.)
Regulatory systems of hormone
production 3.
• Hormonal rhythms. The feedback regulatory
systems are superimposed on hormonal
rhythms that are used for adaptation to the
environment (seasonal changes, the daily
occurence of light-dark cycle, sleep, meals, and
stress)
– Menstrual cycle is repeated on every 28 days
– All pituitary hormone rhythms are entrained to sleep
and to the circadian cycle, generating reproducible
patterns that are repeated appr. every 24 h.
– Other endocrine rhythms occur on a more rapid time
scale. LH and FSH secretion are exquisitely sensitive
to GnRH pulse frequency. Intermittant pulses of
GnRH are required to maintain pituitary sensitivity,
whereas continuous exposure to GnRH causes
pituitary gonadotrop desensitization
Pathologic mechanisms of
endocrine disease 1.
• Hormone excess
– Benign endocrine tumors, including parathyroid, pituitary, and adrenal
adenomas, often retain the capacity to produce hormones, indicating
the fact that they are relatively well differentiated.
• Many tumors exhibit subtle defects in their set points for feedback
regulation (Cushing’s disease, parathyroid adenomas, and autonomously
functioning thyroid nodules)
• Loss of function of a tumor-suppressor gene (menin). MEN1 syndrome
(parathyroid, pancreas islet, and pituitary tumor)
• Activating mutations of RET protooncogene, which encodes a receptor
tyrosine kinase, leads to medullary thyorid carcinoma, pheochromocytoma
and hyperparathyroidism (MEN2)
– Mutations that activate hormone receptors signaling (in several
GPCRs). These mutations induce receptor copuling to Gsα, even in the
absence of hormone Consequently, the adenylate cyclase is activated,
and cyclic AMP levels increase in a manner that mimics hormone action
(LH receptor mutation causes a dominantly transmitted form of male-
limited precocious puberty)
– Autoimmune disorders (Graves’ disease: antibody interactions with the
TSH receptor mimic TSH action, leading to hormone overproduction
Pathologic mechanisms of
endocrine disease 2.
• Hormone deficiency
– Glandular destruction caused by
autoimmunity, surgery, infection, inflammation,
infarction, hemorrhage, or tumor infiltration
– Autoimmun damage : thyroid gland
(Hashimoto’s thyroiditis, type 1 diabetes
mellitus)
– Mutation of hormones, hormone receptors,
transcription factors, enzymes, and channels
Pathologic mechanisms of
endocrine disease 3.
• Hormone resistance
– Inherited defects in membrane receptors, or
the pathway that transduce receptor signals
– Defective hormone action, despite the
presence of increased hormone levels
• Relatively rare genetic forms, such as androgen
receptor mutation in complete androgen
resistance: female phenotypic appearance in
genetic (XY) males
• More common aquired forms: insulin resistance in
type 2 diabetes, leptin resistance in obesity
Hormone measurements and
endocrine testing 1.
• Radioimmunoassay are the most important diagnostic
tool in endocrinology. The use of two different antibodies
to increase binding affintiy and specificity.
• The assays are sensitive enough to detect plasma
hormone concentration in the picomolar to nanomolar
range
• A variety of other techniques are used to measure
specific hormones, including mass spectroscopy, various
forms of chromatography, and enzymatic methods
• The urinary hormone determinations remain useful for
evaluation of some conditions. Collection of the sample
over 24 h provide an integrated assesment of the
hormone production, many of which vary during the day.
Hormone measurements and
endocrine testing 2.
• The normal range for most hormone is relatively
broad, varying by a factor of two to tenfold. The
correct normative database is essential part of
interpreting hormone tests.
• For many endocrine systems, much information
can be gained from basal hormone testing,
when different components of the endocrine
axis are assessed simultaneously.
– Testosterone and LH
– TSH and free thyroxine
– Parathormone and serum calcium
– ACTH and cortisol
Hormone measurements and
endocrine testing 3.
• It is not uncommon, however, for baseline
hormone levels associated with pathologic
endocrine conditions to overlap with the
normal hormone range. In this
circumstance, dynamic testing is useful
for further separate the two gropus:
– Suppression in case of suspected
hyperfunction
– Stimulation in the setting of suspected
hypofunction
Prevalence of endocrine and
metabolic disorders
Disorder Prevalence in adults Testing
Obesity 31% BMI>30 BMI calculation