In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).
A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).\nThe patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.\nExamination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).\nMild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.\nThe patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved.