The main methods of investigation in endocrinology

• Oral glucose tolerance test (OGTT)

Indications:

• borderline fasting or post-prandial blood glucose

• persistent glycosuria

• glycosuria in pregnant women

• pregnant women with a family history of diabetes mellitus and those who previously had large babies or unexplained fetal loss

Glucose tolerance test (GTT)

Fasting serum glucose, mmol/l

2 hours after glucose loading, mmol/l

Capillary blood

Health 3,3 – 5,5 <7,8

Impaired glucose tolerance

5,6 – 6,1 7,8 – 11,1

Diabetes mellitus > 6,1 > 11,1

Impaired fast glucose tolerance

5,6 – 6,1 < 7,8

Screening for diabetes• with typical symptoms of diabetes• __ with a first-degree relative with diabetes• __ who are members of a high risk ethnic group• __ who are overweight (BMI ≥ 25.0 kg/m²)• __ who have delivered a baby >4.5 kg or had

GDM• __ who are hypertensive (≥ 140/90 mmHg)• __ with raised serum triglyceride and cholesterol

levels• __ who were previously found to have IGT or

IFG

• The basic laboratory measures for screening are:

• 1. Fasting capillary blood glucose

• 2. Glucosuria

• 3. HbA1c

• 4. OGTT

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3)

are secreted under the stimulatory influence of pituitary thyrotropin (thyroid-stimulating hormone or TSH). TSH secretion is primary regulated by a dual mechanism:

• thyrotropin-releasing hormone (TRH);

• thyroid hormone.

Thyroid hormone exits in circulation in both free and bound forma. The thyroid gland is the sole source of T4 and only 20% of T3 is secreted in the thyroid. Approximately 80% of T3 in blood is derived from peripheral tissue (mainly hepatic or renal) deiodinatoin of T4 to T3.

Hypothalamus

TRH stimulation

inhibition

Pituitary

TSH stimulation

Thyroid

T4

T3Liver

ThyroidBindingproteins

Free hormone Bound hormone

Diagnosis of toxic diffuse goiterI. Laboratory findings. (The diagnosis of hyperthyroidism is usually straightforward and depends on careful clinical history and

physical examination, a high index of suspection, and routine thyroid hormone determination).

1. In most patients serum total T3 and T4 concentrations, are increased. Elevation of T3 - resin uptake is present.

2. TSN (serum thyroid stimulating hormone) may be decreased, but it is not very sensitive assay in the assessment of thyroid hyperfunction.

3. If the diagnosis of hyperthyroidism remains unclear after these initial tests, more expensive, sophisticated and time – consuming tests may be required, e.g. A TRH test

II. Ultrasonography,computed tomography, MRT

Diagnostic of hypothyroidism

1. Blood analysis: anemia; hypercholesterolemia2. Levels of thyroid hormone: both serum T4 and T3

are decreased (but in 25% of patients with primary hypothyroidism may be normal circulating levels of T3), TSH hormone disturbances (in primary hypothyroidism serum levels of TSH are very high (feedback), low level of circulating TSH in secondary)

3. ECG;4. Examination of tendon reflexes5. Ultrasonic examination

Subclinical laboratory hypothyroidism

It is a state in which we can’t find clinical features of

hypothyroidism and euthyroidism is reached by compensatory increasing of TSH secretion and that’s why synthesis and secretion of such level of thyroid hormone that will be enough for organism.

It is an asymptomatic state in which serum T4 and free T4 are normal, but serum TSH is elevated.

Regulation of secretion

• glucocorticoids’ and androgens’ secretion is regulated by hypothalamic – pituitary system

• mineralocorticoids’ secretion is regulated by the renin – angiotensin system, the level of Na+, K+ in blood, and to a lesser extent of ACTH

Laboratory findings in adrenal

insufficiency.1. A low serum Na level and a high serum P level together

with a characteristic clinical picture suggest the possibility of Addison’s disease.

2. Adrenal insufficiency can be specifically diagnosed by:

• low levels of plasma glucocorticoids and mineralocorticoids, or urinary 17 – hydroxycorticosteroid (17 – OHCS) or 17 – ketogenic steroid (17 – KGS);

• demonstrating failure to increase plasma cortisol levels, or urinary 17 – OHCS or 17 – KGS excretion, upon administration of ACTH (in patients with primary adrenal insufficiency, those with secondary adrenocortical insufficiency will have a significant increase in plasma cortisol or 24 - h urinary corticosteroid levels.)

3. To distinguish between primary and secondary adrenal insufficiency, me have to find the level of plasma ACTH: primary shows increased, and secondary shows decreased level.

Instrumental findings.

1. The ECG may decreased voltage and prolonged P – R and Q – T intervals.

2. The EEG shows alized slowing of the α – rhythm.

Catecholamines are produced

from the tyrosine (organism takes it from the meal or from the phenilalanine in the liver) → dioxyphenilalanine (DOPHA) → dopamine (it goes into blood only from some neurons of the central nervous system) → norepinephrine (noradrenaline) (it goes into blood only from sympathetic teleneurons) → epinephrine (adrenaline) (it goes into blood only from adrenal medulla).

The principle urinary metabolic products of epinephrine and norepinephrine are the metanephrines and vanillylmandalic acid (VMA).

Investigations of pheochromocytoma

1. An increased 3-h (24-h) urinary excretion of epinephrine, norepinephrine and their metabolic products (VMA or metanephrines).

2. Increased plasma epinephrine, norepinephrine.

3. CT scanning, MRI of the abdomen for the localization of the tumor.

4. A scan with iodine I 131–labeled metaiodobenzylguanidine (MIBG) is useful for extra – adrenal tumors.

The pituitary gland is the “master gland”, which lies in a bony structure, the sella turcica, located at the base of the skull. The gland is a small organ about I cm long; it weighs 500 mg and is divided into two parts, anterior (adenohypophysis) and posterior (neurohypophysis).

The anterior pituitary secretes- corticotropin (ACTH)- Prolactin- Somatotropin (growth hormone (GH)- gonadotropins [follicle-stimulating (FSH) and

luteinizing (LH) hormones]- thyrotropin (TSH)- melanocyte-stimulating hormones (MSH).In the nerve endings of the posterior pituitary are

stored - Vasopressin (antidiuretic hormone, ADH)- Oxytocin

The hypothalamus plays an important role in hormone regulation by secreting a series of small peptides which stimulate or inhibit the synthesis and release of hormones by the anterior

pituitary• First hypothalamic releasing hormone identified in 1970 was TRH by Schalli and Guilemin who von Nobel prize in medicine for their discoveries in1977

• Realising Inhibiting- CRG- TRG- LGRG- FSRG- GRH - GIH (somatostatin)- PRG - PIF (dopamine)- MRG - MIH

Regulation

• FEEDBACK:

Hormone secretion → delivery to target cells → hormone recognition by receptors in target cells → biologic effect → hormone degradation → signal from target cells to stop further hormone secretion

Diagnosis of acromegaly :

Laboratory investigations:- The level of GH (0,5 – 5,0 ng/ml)- Somatomedin-C- Test with glucose suppression of

growth-hormone secretion- Test with TRH- GTT

3. Enlargement of the sella turcica (90 % of patients) X-ray, CT,MRT

4. Visual - field defects (bitemporal hemianopsia)

Diagnosis of diabetes insipidus

Laboratory signs:- a specific gravity of less than 1,005

- an osmolality of less than 100 mosmol/kg

- serum osmolality is increased.

- level of ADH can be decreased