What workup is recommended for a 60-year-old male with adrenal insufficiency, Crohn's disease, chronic kidney disease (CKD) stage 3A, and hypogonadism on testosterone therapy, presenting with worsening fatigue, trouble staying awake, polyuria, and polydipsia, while on prednisone and Skyrizi (ustekinumab)?

From the Guidelines

For a 60-year-old male with this complex medical history presenting with worsening fatigue, trouble staying awake, polyuria, and polydipsia, I strongly recommend a comprehensive workup focusing on several key areas to rule out potential life-threatening conditions and improve his quality of life. Given his history of adrenal insufficiency, Crohn's disease, CKD stage 3A, and hypogonadism on testosterone therapy, and recent initiation of Skyrizi, it is crucial to consider the potential impact of these conditions and medications on his current symptoms. Initial evaluation should include:

• Fasting blood glucose and HbA1c to assess for new-onset diabetes or steroid-induced hyperglycemia, as suggested by 1 and 1
• Complete metabolic panel to evaluate electrolyte abnormalities, particularly sodium, potassium, and calcium levels, as well as to reassess kidney function given his CKD stage 3A
• Adrenal function testing, including morning cortisol and ACTH levels, to determine if his adrenal insufficiency is adequately managed on current prednisone dosing, considering the guidance on adrenal insufficiency management from 1 and 1
• Thyroid function tests (TSH, free T4) to assess for thyroid dysfunction, which can mimic or exacerbate his symptoms
• Testosterone levels to ensure appropriate replacement therapy, as both under and over-replacement can cause fatigue
• Urinalysis and urine osmolality to evaluate polyuria, while serum osmolality can assess for diabetes insipidus versus diabetes mellitus
• Inflammatory markers (CRP, ESR) and a complete blood count to assess for disease flare or medication-related side effects from his Crohn's disease and Skyrizi therapy
• Medication review to identify potential interactions between his multiple therapies that could be contributing to his symptoms To rule out diabetes insipidus (DI), a water deprivation test or a desmopressin stimulation test should be considered, as recommended by endocrinology guidelines, to assess his body's ability to concentrate urine and respond to desmopressin, respectively. Additionally, given his history of possible pituitary microadenoma, pituitary function tests, including prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone (FSH/LH) levels, should be performed to evaluate for any potential pituitary dysfunction, as suggested by 1 and 1. It is essential to prioritize these tests to determine the underlying cause of his symptoms and guide appropriate management to improve his morbidity, mortality, and quality of life.

From the FDA Drug Label

Desmopressin acetate is contraindicated in patients with the following conditions due to an increased risk of hyponatremia: Moderate to severe renal impairment defined as a creatinine clearance below 50 mL/min Desmopressin acetate can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death

The patient has CKD stage 3A, which may increase the risk of hyponatremia with desmopressin acetate. Given the patient's symptoms of worsening fatigue, trouble staying awake, polyuria, and polydipsia, the differential diagnoses include:

• Diabetes insipidus (DI):
  • Workup suggestions:
    • Water deprivation test: to assess the patient's ability to concentrate urine
    • Desmopressin stimulation test: to evaluate the patient's response to desmopressin
    • Serum sodium and osmolality: to evaluate electrolyte imbalance
    • Urine osmolality: to assess the patient's ability to concentrate urine
• Adrenal insufficiency:
  • Workup suggestions:
    • Corticosteroid levels: to evaluate adrenal function
    • ACTH stimulation test: to assess adrenal reserve
• Hypogonadism:
  • Workup suggestions:
    • Testosterone levels: to evaluate gonadal function
    • Gonadotropin levels: to assess pituitary function
• Pituitary dysfunction:
  • Workup suggestions:
    • Pituitary hormone levels: to evaluate pituitary function
    • Imaging studies: to assess pituitary anatomy To rule out DI, a water deprivation test or desmopressin stimulation test can be performed 2, 2. However, given the patient's CKD stage 3A, desmopressin acetate is contraindicated due to the increased risk of hyponatremia. Therefore, alternative diagnostic approaches should be considered.

From the Research

Differential Diagnoses and Workup Suggestions

The patient's symptoms of worsening fatigue, trouble staying awake, polyuria, and polydipsia can be attributed to several potential causes. The following differential diagnoses and workup suggestions are recommended:

• Adrenal insufficiency:
  • Check morning cortisol levels to assess adrenal function 3, 4
  • Consider an ACTH stimulation test to evaluate adrenal reserve
• Diabetes insipidus (DI):
  • Water deprivation test to differentiate between central DI, nephrogenic DI, and primary polydipsia 3, 4, 5
  • Measure urine osmolality, serum osmolality, and copeptin levels to aid in diagnosis
• Chronic kidney disease (CKD) progression:
  • Monitor serum creatinine, electrolyte levels, and urine output to assess kidney function
  • Consider a renal ultrasound to evaluate kidney structure and function
• Testosterone therapy effects:
  • Monitor testosterone levels to ensure therapeutic range
  • Assess for signs of testosterone excess or deficiency
• Skyrizi (ustekinumab) side effects:
  • Monitor for potential side effects such as infection, malignancy, or immune-mediated reactions
  • Consider adjusting or discontinuing the medication if side effects are suspected
• Pituitary microadenoma:
  • Consider an MRI of the pituitary gland to evaluate for potential tumor growth or compression
  • Monitor hormone levels, including ACTH, TSH, and prolactin, to assess pituitary function

Workup to Rule Out Diabetes Insipidus

To rule out DI, the following workup is recommended:

• Water deprivation test:
  • Measure urine osmolality, serum osmolality, and copeptin levels at baseline and after water deprivation 3, 4, 5
  • Use a cut-off value of < 400 mosmol/kg in urine and > 302 mosmol/kg in serum to differentiate between DI and non-DI 5
• Arginine vasopressin (AVP) levels:
  • Measure AVP levels to aid in differentiating between central DI and nephrogenic DI 4
• Copeptin levels:
  • Measure copeptin levels to aid in differentiating between central DI and primary polydipsia 4
• Imaging studies:
  • Consider an MRI of the pituitary gland to evaluate for potential tumor growth or compression
  • Consider a renal ultrasound to evaluate kidney structure and function

Fatigue Evaluation

The patient's fatigue can be evaluated using a comprehensive history and physical examination, including:

• Cardiopulmonary, neurologic, and skin examinations to guide the workup and diagnosis 6
• Assessment of sleep hygiene, diet, and energy expenditure to address physiologic fatigue
• Treatment of underlying conditions, such as adrenal insufficiency or CKD, to improve secondary fatigue
• Consideration of cognitive behavior therapy, exercise therapy, or acupuncture to address chronic fatigue 6