A combination of clinical findings and laboratory tests are used to diagnose Rabson-Mendenhall Syndrome. Initially, individuals are screened for symptoms and have their blood sugar levels analyzed. The two principle tests used to determine insulin resistance are the fasting plasma glucose test (FPG) and the oral glucose tolerance test (GTT). Results from a patient with severe insulin resistance will show values exceeding healthy ranges (≤99 mg/dL for FPG and ≤139 mg/dL for GTT) by over 50 units. A genetic history is also established to determine risk of recurrence in the family. Based on the combination of these findings, an appropriate diagnosis is made.

Rabson–Mendenhall syndrome is commonly associated with Donohue syndrome, also known as "Leprechaunism". Both diseases are autosomal recessive disorders caused by mutations on chromosome 19. Severe insulin resistance and an irregular enlargement of the genitalia are also overlapping symptoms.

Diagnosis is made comprehensively, together with visual observation, body fat assessment, a review of lab panels consisting of A1c, glucose, lipid, and patient history.

Caliper measurements of skinfold thickness is recommended to quantify fat loss as a supportive information. In this measurement, skinfold thickness of less than 10mm for men and 22mm for women at the anterior thigh is suggestive cutoff for the diagnosis of lipodystrophy. Less commonly, biphotonic absorptiometry and magnetic resonance imaging (MRI) can be done for the measurement of body fat.

Other forms of insulin resistance may be assessed for differential diagnosis. Resistance to conventional therapy for hyperglycemia and hypertriglyceridemia serves as an indication for lipodystrophy. Specifically, the diagnosis is strongly considered for those requiring ≥200 units/day of insulin and persistent elevation of ≥250 mg/dl of triglyceride levels.

The use of leptin levels should be carefully approached. While low leptin levels are helpful for making the diagnosis, they are not specific for the lipodystrophy. High leptin levels can help excluding the possible lipodystrophy, but there is no well-established standardized leptin ranges.

Rabson and Mendenhall described 3 sibling (2 girls, 1 boy) who initially presented with dental and skin abnormalities, abdominal distention, and phallic enlargement. The children demonstrated early dentition, a coarse, senile-appearing , and striking hirsutism. An "adult growth of hair of head" at 5 years of age was pictured in the case of one of the girls. In the older girl the genitalia were large enough at the age of 6 months to permit vaginal examination for diagnosis of a left ovarian tumor which was removed soon afterward. The children were mentally precocious. Prognathism and very thick fingernails as well as acanthosis nigricans were also described. Insulin-resistant diabetes developed, and the patients died during childhood of ketoacidosis and intercurrent infections. At autopsy pineal hyperplasia was found in all three.

Biologically, infants display fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia, which progress to permanent hyperglycemia and recurrent diabetic ketoacidosis.

Initial and general approach for AGL patients are to treat the metabolic complications such as leptin-replacement therapy and/or to control the abnormal levels of lipids or glucose levels. Anti-diabetic medications such as insulin, metformin, or thiazolidinediones are used for insulin-resistance or high glucose levels, or statins or fibrates are used for hyperlipidemia. If symptoms persist, metreleptin can be prescribed.

Metreleptin (MYALEPT) is a recombinant human leptin analog and was approved by FDA in 2014 for generalized lipodystrophy as an adjunct therapy to diet to treat the complication of leptin deficiency. It is the only drug option approved for generalized lipodystrophy-related symptoms and is not intended to use for patients with HIV-related lipodystrophy or complications of partial lipodystrophy. Although it is a recombinant human leptin analog, it is not completely the same as natural leptin as it is produced in "e. coli" and has added methionine residues at is amino terminus. It works by binding to the human leptin receptor, ObR, and activates the receptor. The receptor belongs to the Class I cytokine family and signals the JAK/STAT pathway. It is available as 11.3 mg powder in a vial for subcutaneous injection upon reconstitution and needs to be protected from the light. For treatment, patients and their doctors need to be enrolled and certified in the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program because people on this treatment has a risk of developing anti-metreleptin antibodies that decrease the effectiveness of metreleptin, and increased risk of lymphoma. Clinical study with GL patients who took metreleptin had increased insulin sensitivity, as indicated by decreased HbA1c and fasting glucose level, and reduced caloric intake as well as fasting triglyceride levels.

Plasmapheresis was previously an option for lowering extremely high triglyceride levels for preventing pancreatitis and painful xanthoma, but its use has been decreased after the approval of metreleptin.

Cosmetic treatments, such as facial reconstruction or implants, can be done to replace adipose tissues.

Lifestyle modifications are also recommended, including changes into less fat diet and exercise.

The prognosis of the disease is unknown as of December, 2017.

The standard test for growth hormone deficiency is the growth hormone stimulation test. Peak levels of growth hormone below normal are considered confirmation of a growth hormone deficiency. Growth-impaired children with a normal stimulation test were considered suspect for having the Kowarski syndrome that may benefit from treatment with growth hormone.

Zadik et al. reported in 1990 that the growth hormone stimulation test is not reliable, suggesting the use of the more reliable 24-hour integrated concentration of growth hormone (IC-GH) as a better test. In 1995, they also suggested that some cases of the neurosecretory growth failure syndrome might have the Kowarski syndrome.

Albertsson-Wikland Kerstin confirmed in 1992 that the IC-GH test is a reproducible test for growth hormone deficiency and Carel et al. confirmed in 1997 that the reliability of the growth hormone stimulation tests was poor.

A 1987 study by Bistrizer et al suggested a diagnostic procedure that may be used to diagnose the Kowarski syndrome. Their study was based on the requirement for the growth hormone molecule to bind a specific binding molecule on the wall of the responsive cells to elicit its activity. Their study demonstrated a decrease ability of the growth hormone from children with the Kowarski syndrome to bind with living IM-9 cells. The test involved measuring the ratio between the levels of growth hormone by a radioreceptor assay (RRA-GH) to the level of growth hormone determined by the established radioimmunoassay (RIA-GH). The study found that the RRA-GH/RIA-GH ratio in NS subjects was normal but significantly below normal (P<0.005) in the Kowarski syndrome patients. The authors proposed the use of their test for the diagnosis of the Kowarski syndrome.

Bistrizer, Chalew and Kowarski demonstrated in 1995 that a modified RRA-GH/RIA-GH ratio test was a predictor for the responsiveness of growth-impaired children to growth hormone therapy.

The RRA-GH/RIA-GH ratio assay proposed by Bistrizer et al. can be used for screening of patients who may have the Kowarski syndrome thus more likely to respond to Growth Hormone therapy. Advances in the methodology for identifying spot mutations in the DNA of individuals demonstrated that the "Kowarski Syndrome is caused by various mutations in the GH1 gene (17q22-q24) that result in structural GH anomalies and a biologically inactive molecule." Testing individual patient for such mutation is offered on the Internet.

Testing the general population under the age of 40 without symptoms is of unclear benefit.

Exclusive breast-feeding is recommended in all newborn infants for its nutritional and other beneficial effects. Parents changing the diet and lifestyle of their offspring by offering appropriate food portions, increasing physical activity, and keeping sedentary behaviors at a minimum may also decrease the obesity levels in children.

If children were more mobile and less sedentary, the rate of obesity would decrease. Parents should recognize the signs and encourage their children to be more physically active. By walking or riding a bike, instead of using motorised transport or watching television, will reduce sedentary activity.

Many organizations have published reports pertaining to obesity. In 1998, the first US Federal guidelines were published, titled "Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report". In 2006 the Canadian Obesity Network published the "Canadian Clinical Practice Guidelines (CPG) on the Management and Prevention of Obesity in Adults and Children". This is a comprehensive evidence-based guideline to address the management and prevention of overweight and obesity in adults and children.

In 2004, the United Kingdom Royal College of Physicians, the Faculty of Public Health and the Royal College of Paediatrics and Child Health released the report "Storing up Problems", which highlighted the growing problem of obesity in the UK. The same year, the House of Commons Health Select Committee published its "most comprehensive inquiry [...] ever undertaken" into the impact of obesity on health and society in the UK and possible approaches to the problem. In 2006, the National Institute for Health and Clinical Excellence (NICE) issued a guideline on the diagnosis and management of obesity, as well as policy implications for non-healthcare organizations such as local councils. A 2007 report produced by Derek Wanless for the King's Fund warned that unless further action was taken, obesity had the capacity to cripple the National Health Service financially.

Comprehensive approaches are being looked at to address the rising rates of obesity. The Obesity Policy Action (OPA) framework divides measure into 'upstream' policies, 'midstream' policies, 'downstream' policies. 'Upstream' policies look at changing society, 'midstream' policies try to alter individuals' behavior to prevent obesity, and 'downstream' policies try to treat currently afflicted people.

The main treatment for obesity consists of dieting and physical exercise. Diet programs may produce weight loss over the short term, but maintaining this weight loss is frequently difficult and often requires making exercise and a lower food energy diet a permanent part of a person's lifestyle.

In the short-term low carbohydrate diets appear better than low fat diets for weight loss. In the long term; however, all types of low-carbohydrate and low-fat diets appear equally beneficial. A 2014 review found that the heart disease and diabetes risks associated with different diets appear to be similar. Promotion of the Mediterranean diets among the obese may lower the risk of heart disease. Decreased intake of sweet drinks is also related to weight-loss. Success rates of long-term weight loss maintenance with lifestyle changes are low, ranging from 2–20%. Dietary and lifestyle changes are effective in limiting excessive weight gain in pregnancy and improve outcomes for both the mother and the child. Intensive behavioral counseling is recommended in those who are both obese and have other risk factors for heart disease.

Five medications have evidence for long-term use orlistat, lorcaserin, liraglutide, phentermine–topiramate, and naltrexone–bupropion. They result in weight loss after one year ranged from 3.0 to 6.7 kg over placebo. Orlistat, liraglutide, and naltrexone–bupropion are available in both the United States and Europe, whereas lorcaserin and phentermine–topiramate are available only in the United States. European regulatory authorities rejected the latter two drugs in part because of associations of heart valve problems with lorcaserin and more general heart and blood vessel problems with phentermine–topiramate. Orlistat use is associated with high rates of gastrointestinal side effects and concerns have been raised about negative effects on the kidneys. There is no information on how these drugs affect longer-term complications of obesity such as cardiovascular disease or death.

The most effective treatment for obesity is bariatric surgery. The types of procedures include laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, vertical-sleeve gastrectomy, and biliopancreatic diversion. Surgery for severe obesity is associated with long-term weight loss, improvement in obesity related conditions, and decreased overall mortality. One study found a weight loss of between 14% and 25% (depending on the type of procedure performed) at 10 years, and a 29% reduction in all cause mortality when compared to standard weight loss measures. Complications occur in about 17% of cases and reoperation is needed in 7% of cases. Due to its cost and risks, researchers are searching for other effective yet less invasive treatments including devices that occupy space in the stomach.

Obesity in children is treated with dietary changes and physical activity. Dieting and missing meals should; however, be discourage. The benefit of tracking BMI and providing counselling around weight is minimal.

The discovery of the Kowarski syndrome created a dilemma. The first diagnostic test for the syndrome was subjecting the suspected children to six month of growth hormone therapy. Kowarski syndrome was assumed to be a very rare disorder (officially recognized as an “orphan disease”). Researchers could not justify subjecting children to a trial period of growth hormone therapy to confirm the diagnosis of a rare syndrome. There is a need for a reliable and practical diagnostic procedure for the syndrome.

Lipodystrophy can be caused by metabolic abnormalities due to genetic issues. These are often characterized by insulin resistance and are associated with metabolic syndrome.

People with Laron syndrome have strikingly low rates of cancer and diabetes, although they appear to be at increased risk of accidental death due to their stature.

A lipodystrophy can be a lump or small dent in the skin that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with diabetes, using purified insulins may also help.

One of the side-effects of lipodystrophy is the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma that can cause bleeding that, in turn, will reject the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the medical condition to worsen.

In some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.

Those affected with deficiency of the interleukin-1–receptor antagonist can have diagnosis achieved via noting an increase of erythrocyte sedimentation rate, as well as the following:

- Genetic test

- Radiological findings

- Clinical findings

Hypoalphalipoproteinemia is a high-density lipoprotein deficiency, inherited in an autosomal dominant manner.

It can be associated with LDL receptor.

Associated regions and genes include:

Niacin is sometimes prescribed to raise HDL levels.

Administration of GH has no effect on IGF-1 production, therefore treatment is mainly by biosynthetic IGF-1. IGF-1 must be taken before puberty to be effective.

The drug product Increlex (mecasermin), developed by the company Tercica, now Genentech, was approved by the US Food and Drug Administration in August 2005 for replacing IGF-1 in patients who are deficient.

IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was approved by the U.S. Food and Drug Administration (FDA) in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion. Side effects from IPLEX are hypoglycemia. IPLEX's manufacturing company, Insmed, after selling its protein production facility, can no longer develop proteins, thus can no longer manufacture IPLEX as of a statement released in July 2009.

For treatment of type II, dietary modification is the initial approach, but many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrates (peroxisome proliferator-activated receptor-alpha agonists) may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy and rhabdomyolysis, so is only done under close supervision. Other agents commonly added to statins are ezetimibe, niacin, and bile acid sequestrants. Dietary supplementation with fish oil is also used to reduce elevated triglycerides, with the greatest effect occurring in patients with the greatest severity. Some evidence exists for benefit of plant sterol-containing products and omega-3 fatty acids.

In terms of treatment a 2013 review indicates that colchicine can be used for DIRA. Additionally there are several other management options such as anakinra, which blocks naturally occurring IL-1, this according to a 2016 pediatric textbook.

Patients show markedly low immunoglobulin levels of IgG, IgA, and IgM.

According to the 2007 AHRQ National Inpatient Sample, in a projected 129,164 hospital encounters in the United States, cachexia was listed as at least one of up to 14 recorded diagnosis codes based on a sample of 26,325 unweighted encounters. A sample of 32,778 unweighted US outpatient visits collected by the CDC's National Ambulatory Medical Care Survey did not list any visits where cachexia was one of up to three recorded diagnoses treated during the visit.

As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

Autoantibodies to the thyroid gland may be detected in various disease states. There are several anti-thyroid antibodies, including anti-thyroglobulin antibodies (TgAb), anti-microsomal/anti-thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb).

- Elevated anti-thryoglobulin (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) can be found in patients with Hashimoto's thyroiditis, the most common autoimmune type of hypothyroidism. TPOAb levels have also been found to be elevated in patients who present with subclinical hypothyroidism (where TSH is elevated, but free T4 is normal), and can help predict progression to overt hypothyroidism. The American Association Thyroid Association thus recommends measuring TPOAb levels when evaluating subclinical hypothyroidism or when trying to identify whether nodular thyroid disease is due to autoimmune thyroid disease.

- When the etiology of hyperthyroidism is not clear after initial clinical and biochemical evaluation, measurement of TSH receptor antibodies (TSHRAb) can help make the diagnosis. In Grave's disease, TSHRAb levels are elevated as they are responsible for activating the TSH receptor and causing increased thyroid hormone production.

This is a form of dysautonomia but differentiated from familial dysautonomia by a lack of familial dysautonomic symptoms such as loss of sense of pain and smell. While L-threo-DOPS has been described as being "very effective for restoring noradrenergic tone and correcting postural hypotension, response to treatment is variable and the long-term and functional outcome is unknown."

Researchers have put together retrospective data collections in order to better under the progression of this orphan disease. Most studies show a perinatal period marked by inadequacy of the ANS to control blood pressure, blood sugar, and body temperature. The experiences of orthostatic hypotension, exercise intolerance, and "traumatic morbidity related to falls and syncope" have been documented later in lives of people with this condition. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation, outcome of these diseases, their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies, a patient registry was established by the non-commercial International Working Group on Neurotransmitter Related Disorders (iNTD).

Recent studies have explored the connection between DβH deficiency, Droxidopa treatment, and the effect on orthostatic tolerance and glucose homeostasis. It was found that Droxidopa increased acute and late glucose-stimulated insulin secretion and improved patients' insulin sensitivity. However, the use of Droxidopa was found to only produce "modest changes in glucose homeostasis" overall. This shows that treatment modalities other than Droxidopa should be pursued as possible adjuncts for the hyperinsulinemia seen in DβH deficiency.