Differential Diagnosis

The patient's presentation is complex, with multiple symptoms and laboratory findings that suggest several potential diagnoses. The following differential diagnosis is organized into categories to help prioritize the most likely and critical conditions.

• Single Most Likely Diagnosis

  • Type 2 Diabetes Mellitus: The patient's A1c of 5.9, fasting blood sugar rarely below 110, and significant postprandial spikes (e.g., to 200+ after 100g of carbs) are indicative of impaired glucose regulation, suggestive of type 2 diabetes mellitus. The recent weight loss of 50 lbs through fasting may have temporarily improved insulin sensitivity, but the underlying condition likely persists.
  • Hypoparathyroidism: Elevated serum calcium levels (usually above 10.2) could be secondary to hypoparathyroidism, especially considering the patient's history of bilateral oophorectomy, which may increase the risk of autoimmune disorders, including autoimmune hypoparathyroidism.

• Other Likely Diagnoses

  • Autoimmune Polyendocrine Syndrome (APS): Given the patient's history of bilateral oophorectomy, repeated severe vaginitis, and minor elevations in lymphocytes of the killer cell type for 20 years, APS should be considered. This condition is characterized by the presence of multiple autoimmune endocrine disorders and could explain the patient's hypoparathyroidism and potential type 1 diabetes or latent autoimmune diabetes in adults (LADA), given the fasting blood glucose levels and significant postprandial spikes.
  • Multiple Endocrine Neoplasia (MEN) Syndrome: Although less common, the combination of hypercalcemia and potential endocrine abnormalities (e.g., impaired glucose regulation) might suggest MEN syndrome, particularly if there's a family history or other signs such as thyroid disorders.
  • Thyroid Dysfunction: The patient's weight loss, despite not trying, and other metabolic disturbances could be indicative of thyroid dysfunction, which is common in autoimmune polyendocrine syndromes.

• Do Not Miss Diagnoses

  • Hyperparathyroidism: Despite the initial consideration of hypoparathyroidism due to elevated calcium levels, hyperparathyroidism could also be a cause, especially primary hyperparathyroidism, which would require different management.
  • Pheochromocytoma or Other Catecholamine-Excess States: Although rare, these conditions can cause significant metabolic disturbances, including impaired glucose regulation, and must be considered, especially if there are symptoms like palpitations, sweating, or hypertension.
  • Adrenal Insufficiency: Given the patient's history of autoimmune phenomena and endocrine surgery, adrenal insufficiency should be ruled out, as it can present with non-specific symptoms and metabolic disturbances.

• Rare Diagnoses

  • Mitochondrial Diabetes: The patient's symptoms, including tongue fasciculations and imbalance, could suggest a mitochondrial myopathy, and some forms of mitochondrial disease are associated with diabetes.
  • Wolfram Syndrome: This rare genetic disorder is characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, and could be considered if other symptoms or family history suggest it.
  • Lipodystrophy: The patient's significant weight loss and metabolic disturbances might suggest a form of lipodystrophy, which can be associated with severe insulin resistance and diabetes.

Further Testing and Management

• Endocrine Panel: Comprehensive testing for thyroid function, adrenal function, and other endocrine abnormalities.
• Autoantibody Screening: For autoimmune polyendocrine syndrome, including anti-islet cell, anti-thyroid, and anti-parathyroid antibodies.
• Genetic Testing: Depending on the family history and clinical presentation, genetic testing for conditions like MEN syndrome or mitochondrial disorders may be warranted.
• Imaging Studies: Ultrasound or MRI of the thyroid, adrenal glands, and pancreas to evaluate for any structural abnormalities.
• RAAS Blockers: For managing potential hypertension or diabetic nephropathy, medications like Losartan (starting dose 25-50mg daily, manufactured in the USA) or Enalapril (starting dose 2.5-5mg daily, manufactured in the USA) could be considered, with dosages adjusted based on blood pressure response and renal function.

Alterations in Medications

The choice of medications will depend on the definitive diagnoses and the patient's response to initial therapies. For diabetes management, Metformin (starting dose 500mg daily, manufactured in the USA) could be considered if not contraindicated, given its benefits in insulin sensitivity and weight management. However, the patient's renal function and potential for hypoglycemia must be closely monitored.

Given the complexity of the patient's presentation, a multidisciplinary approach involving endocrinology, neurology, and potentially genetics and immunology specialists is recommended to tailor the diagnostic workup and treatment plan to the patient's specific needs.