Approach to the Patient with Endocrine Disorders PDF

Approach to the Patient with Endocrine Disorders Chala T(MD)  Outline Introduction History Taking Physical Examination Laboratory Investigation Imaging Treatment  Objectives At end of this session students able to:- – Take history and do P/...

Approach to the Patient with Endocrine Disorders Chala T(MD)  Outline Introduction History Taking Physical Examination Laboratory Investigation Imaging Treatment  Objectives At end of this session students able to:- – Take history and do P/E in Pt with Endocrine disorder – Do Basic Work up in Pt with Endocrine disorder – Describe management principle of in Pt with Endocrine disorder  Introduction Endocrinology is the study of glands and the hormones they produce Unlike many other specialties in medicine, it is not possible to define endocrinology strictly along anatomic lines. The classic endocrine glands—pituitary, thyroid, parathyroid, pancreatic islets, adrenals, and gonads Introduction… Introduction… Introduction…  Introduction… The endocrine system co-ordinates the body´s internal physiology, regulates its development throughout life, and helps it to adapt to nutrition and other external environmental changes. The system is based on a number of glands, which secrete hormones into internal medium to act on target tissues. Hormones first interact with specific high-affinity receptors in the cells, or on the cells of target tissues. Receptor activation then initiates a cascade of linked biochemical reactions within the cells, that produce the specific response.  Introduction… Hormones – active molecules Hormones are biologically high active drugs of the body which control the metabolic activity all different tissues and organs in the body. They play an important role in development and growth of the body, they control the reproduction mechanisms, they help how to adapt on everyday life-stress and how to survive.  Introduction… Endocrinology concerns the synthesis, secretion and action of hormones. Hormones represent chemical messengers - diverse molecular structures (proteins, peptides, steroids) – are released from endocrine glands – coordinate the activities of many different cells. Endocrine diseases – heterogeneous group – wide range of manifestations affecting many other organs.  Introduction The management of endocrine disorders requires a broad understanding of intermediary metabolism, reproductive physiology, bone metabolism, and growth. The practice of endocrinology is intimately linked to a conceptual framework for understanding hormone secretion, hormone action, and principles of feedback control  Introduction… The endocrine system is evaluated primarily by measuring hormone concentrations, arming the clinician with valuable diagnostic information. Most disorders of the endocrine system are amenable to effective treatment once the correct diagnosis is established.  PATHOLOGIC MECHANISMS OF ENDOCRINE DISEASE Endocrine diseases can be divided into three major types of conditions: – 1. hormone excess – 2.hormone deficiency, and – 3.hormone resistance  Endocrine pathology Arising within the gland is called a primary disease (e.g. primary hypothyroidism in Hashimoto´s thyroiditis) Abnormal stimulation of the gland from pituitary = secondary disease (e.g. secondary hypothyroidism (in patients with pituitary tumour and TSH deficiency). Some endocrine diseases are common: – Thyroid gland disease (occurs in >10% population in areas with iodine deficiency) – Reproductive system diseases – Β-cells of the pancreas – Diabetes mellitus (DM) Type 1  Endocrine Pathology… Endocrine deficiency disorders are treated with physiologic hormone replacement Hormone excess conditions, which usually are caused by benign glandular adenomas, are managed by :- – removing tumors surgically or – reducing hormone levels medically. Causes of Endocrine Dysfunction  Causes Endocrine hyperfunction Hyperfunction of endocrine glands may result from overstimulation by the pituitary whether due to intrinsic pituitary dysfunction or overstimulation of the pituitary by the hypothalamus. However, hyperfunction of endocrine glands is most commonly due to hyperplasia or neoplasia of the gland itself. In some cases, cancers from other tissues can produce hormones (ectopic hormone production). Hormone excess also can result from exogenous hormone administration. In some cases, patients take nonprescription products that contain hormones and may not know or tell the physician.  Causes of Hyperfunction… Tissue hypersensitivity to hormones can occur. Antibodies can stimulate peripheral endocrine glands, as occurs in hyperthyroidism of Graves disease. Disruption of a peripheral endocrine gland can rapidly release stored hormone (eg, thyroid hormone release in subacute thyroiditis). Enzyme defects in the synthesis of a peripheral endocrine hormone can result in overproduction of hormones proximal to the block. Finally, overproduction of a hormone can occur as an appropriate response to a disease state. Causes Endocrine hypofunction Most examples of hormone deficiency states can be attributed to glandular destruction caused by:- – Autoimmunity, – Surgery, – Infection, – Inflammation, – Infarction, – Hemorrhage – Tumor Infiltration  Causes of hormone resistance Mutations in a number of hormones, hormone receptors, transcription factors, enzymes, and channels can also lead to hormone deficiencies Most severe hormone resistance syndromes are due to inherited defects in membrane receptors, nuclear receptors, or the pathways that transduce receptor signals. These disorders are characterized by defective hormone action despite the presence of increased hormone levels. In complete androgen resistance, for example, mutations in the androgen receptor result in a female phenotypic appearance in genetic (XY) males History Taking in endocrine disorder Regardless of whether there is an obvious problem, treat each patient as an unknown in order to avoid missing an endocrine disorder. A patient with one endocrine disease (e.g., Hashimoto's thyroiditis) is at greater risk for the development of other endocrine disorders (e.g., adrenal, testicular, or ovarian failure). A patient may harbor more than one endocrinopathy, which could be overlooked if subtle historical and clinical clues are not seen.  History… Always allow patients to express themselves. Ask patients how they feel and let them answer. Often, within the first few minutes of the history an endocrine cause becomes apparent. I find it most useful to review the patient's complaints literally from head to toe. The patient's vocal pitch may give a clue. A hypogonadal male has a high-pitched voice, while an androgenized female may have a deeper voice than expected.  History… Hair growth is an important piece of information. Ask the patient how often he shaves, and if the frequency has decreased. In the adult male the presence or absence of facial hair and the frequency of shaving give important information as to gonadal status; for example, hypogonadal males with primary (Kallman's syndrome) or secondary gonadal insufficiency (atrophic testicles following trauma, mumps, autoimmune diseases, etc.). Family history can be a clue because many families display sparse facial hair growth. Females may complain of excessive body hair, which should lead you to investigate causes of excessive androgens.  History… The pituitary gland should be investigated through history, physical, and radiographs If you think of the hormones secreted by the pituitary, appropriate questions can be asked Excess ACTH produces the classic Cushing's appearance. Mental changes, fatigue, muscle weakness, easy bruising, infections, stretch marks, and acne are but a few of the findings related to steroid excess. Deficiency of these hormones can produce complaints ranging from fatigue ,dizziness, shock, coma, joint and abdominal complaints.  History… FSH and LH- In the female, the appropriate sequence of adenarche, thelarche, and menarche should be obtained. Amenorrhea is an important clue in a breakdown in the hypothalamic-pituitary–ovarian axis In male with a full beard who has fathered children recently does not have a primary hypogonadal process. The presence of normal erections, adequate libido, and a full beard with a normal male body habitus helps exclude hypogonadism without the need for extensive testing.  History… Thyroid dysfunction can be so mild as to be unnoticed by the patient or examiner. Local effects of thyroid gland enlargement may produce only a goiter. Pain and compression of the surrounding structures can occur  Hx… Hyperthyroidism patients often complain of fatigue, weight loss, and constipation over activity, nervousness, jitterness, Shaking, to heat intolerance , difficulty concentrating, and insomnia. Hypothyroidism may present as loss of interest, depression, fatigue, cool dry skin, constipation, mild degree of weight gain The disorder can progress to the point of extreme and overwhelming hypothermia, coma, and death.  History… DM often presents insidiously with the gradual onset of excessive thirst, urination, nocturnal frequency, weight loss, and increased appetite. Blurring of vision, frequent infections, numb or painful extremities, and nonhealing extremity ulcers are important clues that should lead to a diabetic evaluation  Physical Examination In Endocrine disorder Because most glands are relatively inaccessible, the physical examination usually focuses on the manifestations of hormone excess or deficiency as well as direct examination of palpable glands, such as the thyroid and gonads. The manifestations of endocrine illnesses are so far reaching as to affect almost every organ system. A comprehensive physical examination to complement a complete history is mandatory Examine head to toe  P/E… Astute clinical skills are required to detect subtle symptoms and signs suggestive of underlying endocrine disease. For example, a patient with Cushing’s syndrome may manifest specific findings, such as :- – Central obecity, – Skin striae, and – Proximal muscle weakness, in addition to features seen commonly in the general population  P/E.. Similarly, the insidious onset of hypothyroidism—with mental slowing, fatigue, dry skin, and other features—can be difficult to distinguish from similar, nonspecific findings in the general population. Clinical judgment that is based on knowledge of disease prevalence and pathophysiology is required to decide when to embark on more extensive evaluation of these disorders  P/E… With the patient undressed, observe the body size and habitus The distribution of body fat may reveal information as to nutrition, thyroid and adrenal status, important clues as to the presence of Cushing's disease. The combination of supraclavicular fullness, moon facies, violaceous striae, dorsal cervical fat pad, and a centripetal truncal obesity is often diagnostic. P/E… P/E…  P/E… Scalp and facial hair as well as the balding pattern are useful clues in assessing the patient's gonadal status. Decreased quantities of facial hair, perioral and periorbital wrinkling may be subtle signs of hypogonadism. In the female, excessive hair, acne, male-pattern balding, and central scalp hair loss are signs of androgen excess. P/E…  P/E… Inspect and palpate the thyroid The skilled examiner can often visualize a thyroid nodule or outline a diffusely enlarged gland Gynecomastia in the male may have important clinical significance ranging from hypogonadism to malignancy. P/E…. P/E.. Gynecomastia  P/E… In the male, the genital examination together with peripheral manifestations of gonadal disease may be of high diagnostic yield. One should carefully inspect for the presence of testicles within the scrotum and palpate for size and consistency. In both the male and female, pubic hair patterns are important. Examination of the perineum may yield important information as clitoromegaly or other labial or urogenital abnormalities are noted.  P/E… Careful inspection of the hands and feet, especially in diabetics, is important Shiny thin skin with absence of hair on the lower extremities and absent pulses in the feet suggest the presence of macrovascular or microvascular disease of diabetes mellitus. Proximal muscle weakness is common to other endocrine disorders, such as hyperthyroidism and Cushing's disease.  Laboratory Testing for Endocrine Disorders Because symptoms of endocrine disorders can begin insidiously and may be nonspecific, clinical recognition is often delayed for months or years. For this reason, biochemical diagnosis is usually essential; it typically requires measuring blood levels of the peripheral endocrine hormone, the pituitary hormone, or both. Laboratory testing plays an essential role in endocrinology by allowing quantitative assessment of hormone levels and dynamics.  Lab Ix… Because most hormones have circadian rhythms, measurements need to be made at a prescribed time of day. Hormones that vary over short periods (eg, LH) necessitate obtaining 3 or 4 values over 1 or 2 hours or using a pooled blood sample. Hormones with week-to-week variation (eg, estrogen) necessitate obtaining separate values a week apart.  Lab Ix… Blood hormone measurements Immunoassays are the most important diagnostic tool in endocrinology, as they allow sensitive, specific, and quantitative determination of steady-state and dynamic changes in hormone concentrations Free or bioavailable hormone (ie, hormone not bound to a specific binding hormone) is generally believed to be the active form. These methods can be expensive and time-consuming Analog and competitive free hormone assays, although often used commercially, are not always accurate and should not be used.  Lab Ix… Most hormone measurements are based on plasma or serum samples. However, urinary hormone determinations remain useful for the evaluation of some conditions. Urinary collections over 24 h provide an integrated assessment of the production of a hormone or metabolite, many of which vary during the day. E.g – A 24-h urine creatinine – A 24-h urine-free cortisol  Lab Ix… Dynamic tests In many cases, a dynamic test is necessary. Thus, in the case of hypofunctioning organs, a stimulation test (eg, ACTH stimulation) can be used. In hyperfunction, a suppression test (eg, dexamethasone suppression) can be used.  Imaging Radiologic imaging tests such as computed tomography (CT) scan, magnetic resonance imaging (MRI), thyroid scan, and ultrasound are also used for the diagnosis of endocrine disorders. However, these tests generally are employed only after a hormonal abnormality has been established by biochemical testing.  Pathological Testes FNAC Biopsy Treatment of Endocrine Disorders Replacing deficient hormone Suppressing excessive hormone production Radiation therapy and surgery can used to treat hyper function disorders.  Rx… Hypofunction disorders are usually treated by replacement of the peripheral endocrine hormone regardless of whether the defect is primary or secondary If resistance to the hormone exists, drugs that reduce resistance can be used (eg, metformin for T2DM) Occasionally, a hormone-stimulating drug is used (eg, a sulfonylurea to stimulate insulin secretion). Thank you