Obesity etiology investigation and clinical differential diagnosis process
Identify the cause. The causes of obesity are very complex, but can be divided into two categories: one is a symptom of a certain disease, called symptomatic obesity or secondary obesity; the other is where no specific disease can be found, called simple obesity or obesity syndrome. Diagnosing obesity, like diagnosing any other disease, requires a detailed medical history, a systematic physical examination, and some necessary laboratory tests. When taking a medical history, attention should be paid to the age of onset, the rate of progression, eating habits, and physical activity levels. It is also important to note any family history, as changes in occupation are often associated with obesity.
Based on a comprehensive analysis of the data, it is possible to distinguish whether obesity is secondary obesity or simple obesity. (1) Inquire about medical history: The cause of obesity should be explored, such as whether drugs that can cause obesity have been used, whether there is a history of head trauma, encephalitis, brain abscess, or stroke, whether obesity occurred during the recovery period of acute or chronic diseases, major surgery, or after childbirth, and changes in lifestyle and eating habits, such as stopping physical exercise, changing jobs, relocation, or improvement of nutritional conditions. There are also those who develop the disease after mental stimulation or after suffering from manic-depressive illness.
Endocrine obesity often presents with the chief complaint of the primary disease. Diabetes mellitus commonly presents with thirst, polyuria, and polydipsia; hypothalamic obesity may present with headache, diabetes insipidus, galactorrhea, bulimia, and symptoms of cranial nerve damage; hereditary obesity often presents with incomplete development of sex organs, intellectual disability, and deformities. A patient presenting with decreased appetite but increased weight should raise suspicion of hypothyroidism. Pay attention to the timing and rate of weight gain in the patient's medical history. Childhood obesity is often simple or hereditary obesity, while adult-onset or shorter-term obesity may indicate secondary obesity. Note any accompanying symptoms of obesity.
Conditions such as hypertension, diabetes, and menstrual disorders can be manifestations of underlying diseases that cause secondary obesity, or complications of simple obesity. Women should be asked about their menarche, amenorrhea, and reproductive history. (2) Physical examination: Pay attention to height, weight, muscle development, and whether there is edema or congenital malformation. Pay attention to body shape; women with masculinized fat distribution or men with feminized fat distribution may have hypogonadism. Pay attention to the development of secondary sexual characteristics. Central obesity may be due to Cushing's syndrome; abnormal increase in lower body fat and atrophy of upper body fat may be progressive fat atrophy.
Pay attention to the presence of central nervous system and mental disorders. Hypothalamic obesity may present with visual field defects and cranial nerve damage. Mental disorders accompanied by hypoglycemia may indicate insulinoma. Intellectual disability may be seen in Laurence-Moon-Biedl syndrome, Prader-Willi syndrome, congenital ovarian hypoplasia, and congenital testicular hypoplasia, and may be accompanied by underdeveloped secondary sexual characteristics and reproductive organ development disorders. During the physical examination, attention should also be paid to changes in blood pressure and signs of diabetes. (3) Auxiliary examinations.
① X-ray examination: Plain skull film and tomographic film of the sella turcica. This can detect large pituitary tumors, brain tumors, and hyperplasia of the inner table of the skull. For suspected brain tumors, pneumocephalus or cerebral angiography is performed. For suspected adrenal tumors, retroperitoneal pneumocephalus or angiography can be performed. X-ray examinations of the pancreas and ovaries can also be performed. ② CT and MRI examinations: Head and whole-body CT or MRI examinations can detect pituitary tumors and other intracranial tumors, as well as tumors in the adrenal glands, pancreas, ovaries, etc., and are currently commonly used non-invasive examinations.
③ Ultrasound examination. Helpful in diagnosing tumors or cysts of the adrenal glands, pancreas, thyroid gland, and gonads. ④ Radionuclide examination. Mainly used for diagnosing visceral organ tumors, such as adrenal or thyroid tumors. ⑤ Other chromosome examinations. Can detect hereditary diseases. Visual field examination helps to detect hypothalamic-pituitary lesions. (4) Endocrine function examination. ① Hypothalamic-pituitary-thyroid axis examination. Includes basal metabolic rate (BMR), thyroid ¹³¹I uptake rate, and serum protein-bound iodine (PBI).
Serum total T3, total T4, free T3 (FT3), and free T4 (FT4) are measured to assess thyroid function and detect hypothyroidism. Thyroid-stimulating hormone (TSH) and the TSH stimulation test primarily differentiate between primary and secondary hypothyroidism. Elevated T3 and T4 levels after TSH injection indicate secondary hypothyroidism caused by the hypothalamus or pituitary gland; no response indicates primary hypothyroidism. The thyrotropin-releasing hormone (TRH) stimulation test further differentiates hypothyroidism; no TSH response after TRH injection indicates pituitary hypothyroidism, while a TSH response indicates hypothalamic hypothyroidism.
② Hypothalamic-pituitary-adrenal axis function tests. Measurements of urinary 17-hydroxycorticosteroids, 17-ketocorticosteroids, and urinary free cortisol; plasma cortisol measurement, primarily to detect patients with Cushing's syndrome. Plasma adrenocorticotropic hormone (ACTH) and ACTH stimulation tests, mainly to differentiate whether elevated cortisol is primary in the adrenal glands or secondary to the pituitary and hypothalamus. Low-dose and high-dose dexamethasone suppression tests; the former is used to differentiate between simple obesity and Cushing's syndrome; the latter is used to differentiate whether Cushing's syndrome is primary due to adrenal tumors (Cushing's syndrome) or secondary to pituitary and hypothalamic lesions (Cushing's disease).
③ Hypothalamic-pituitary-gonadal axis function tests. Serum testosterone and estradiol measurements are used to detect hypogonadism. Follicular phase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements, along with the luteinizing hormone-releasing hormone stimulation test, indicate that elevated serum LH and FSH levels suggest primary hypogonadism due to gonadal lesions. Decreased levels suggest secondary hypogonadism due to hypothalamic or pituitary involvement. After LHRH injection, elevated FSH and LH levels indicate a hypothalamic lesion, while no response to FSH and LH indicates a pituitary lesion. ④ Pancreatic function tests.
When diabetes or pancreatic beta-cell tumors are suspected, fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin, and serum fructosamine can be measured. Glucose tolerance tests, starvation tests, and D860 tests can also be used. Diabetes is defined as a fasting blood glucose level ≥7.8 mmol/L (140 mg/dL), or a 2-hour blood glucose level ≥11 mmol/L (200 mg/dL) in a glucose tolerance test. Insulinomas, blood glucose is low, but serum insulin is high; in cases of hypoglycemia induced by starvation tests, insulin levels are high, and the ratio of insulin (µIU/mL) to fasting blood glucose (mg/dL) is greater than 0.5.
3. Make a clear diagnosis. If the above examinations are normal, it can be judged as simple obesity. Combined with the medical history, it can be divided into constitutional obesity and nutritional obesity. (1) Constitutional obesity: also known as childhood-onset obesity, is caused by the proliferation of fat cells and is related to excessive nutrition before the age of 25. It is often accompanied by a family history of heredity. Overweight children usually become overweight adults. From the 30th week of fetal development to 1.5 years after birth, fat cells have a very active period of proliferation, called the "sensitive period".
Excessive nutrition during this period can lead to an increase in fat cells. Therefore, it is very important for children, especially those under 10 years old, to maintain a normal weight. This type has the following characteristics: ① Family history of obesity. ② Obesity since childhood. ③ Uniform obesity throughout the body, with fat cells showing hyperplasia and hypertrophy. ④ Poor efficacy of dietary restriction and exercise, and less sensitivity to insulin. (2) Nutritional obesity: also known as acquired (exogenous) obesity, mostly due to excessive nutrition after the age of 20 to 25, with the intake of calories exceeding the needs of various metabolic activities of the body.
Obesity can be caused by insufficient physical activity or prolonged bed rest for some reason, leading to low energy expenditure. Its characteristics include: ① Onset between 20 and 25 years of age; ② Predominantly limb obesity, with enlarged fat cells but no hyperplasia; ③ Dietary control and exercise are relatively effective, and insulin sensitivity can return to normal after treatment. Constitutional obesity can also recur with acquired obesity, becoming a mixed type. Both of these types of obesity are collectively referred to as simple obesity, particularly common in urban women aged 20-30, although spontaneous obesity is also a tendency in middle-aged men and women.