A 38-year-old female presents to the OPD at 1 PM with complaints of low back pain for the past 4 months. Her generalised muscle weakness has been progressively worsening over the last month and is starting to worry her. She reports a recent loss of interest in her usual activities and experiences fatigue even without exertion.
She was diagnosed with type II diabetes mellitus in her late 20s and has been taking insulin regularly since then. She also reports irregular menstrual cycles for the past 2 years, along with unexplained abdominal weight gain.
Vitals:
HR: 74 bpm | BP: 154/96 mmHg | RR: 16/min
Co-morbidities: Obesity, Hypertension, Type II Diabetes Mellitus
A senior sitting next to you notices that you are increasing the patient’s insulin dose without proper evaluation. He advises you to conduct proper assessment first.
On examination: No pallor, icterus, clubbing, cyanosis, lymphadenopathy, or edema.
Systemic examination reveals:
• Purple/pink striae on arms, abdomen, and thighs
• Multiple bruises and cuts on arms and hands (thin fragile skin)
• Obesity with prominent fat deposition over upper back and trunk
• Proximal muscle weakness in both lower limbs
• Not on steroid therapy
Examination Findings:
No pallor, icterus, clubbing, cyanosis, lymphadenopathy, or edema.
Systemic examination reveals:
• Purple/pink striae on arms, abdomen, and thighs
• Multiple cuts and bruises (attributed to thin skin)
• Obesity with fat deposition over upper back and trunk
• Proximal muscle weakness in both lower limbs
• Not on steroid medication
A senior intervenes - you are prescribing steroids without proper indications. He advises complete evaluation.
Examination reveals:
• Purple-pink striae on arms, abdomen, thighs
• Multiple cuts and bruises (thin skin)
• Obesity with fat deposition over upper back and abdomen
• Proximal muscle weakness in lower limbs
• Not on steroid therapy
Results: UPT negative, Fasting blood sugar: 120 mg/dL (normal)
Physical examination revealed:
• Purple/pink striae on arms, abdomen, thighs
• Multiple cuts and bruises (thin skin)
• Obesity with fatty deposits in upper back and midsection
• Proximal muscle weakness in lower limbs
• Not taking steroids
Your senior interrupts - midnight serum values are more useful for diagnosis. You admit the patient and wait until midnight.
Midnight values:
• Serum cortisol: 2.5 µg/dL (normal ≤ 1.8)
• Salivary cortisol: 6 nmol/L (normal ≤ 5.5)
You suspect Cushing syndrome and order 8 AM plasma cortisol level.
This investigation is important to rule out what condition?
Midnight values:
• Serum cortisol: 2.5 µg/dL (normal ≤ 1.8)
• Salivary cortisol: 6 nmol/L (normal ≤ 5.5)
You suspect Cushing syndrome and order 8 AM plasma cortisol level.
This investigation is important to rule out what condition?
Lab results:
• WBC: 14,800/µL (Leukocytosis)
• Neutrophils: 86% (Neutrophilia)
• Lymphocytes: 10% (Lymphopenia)
• Sodium: 148 mEq/L (Hypernatremia)
• Potassium: 3.2 mEq/L (Hypokalemia)
• pH: 7.48, pCO₂: 46 mmHg, HCO₃⁻: 32 mEq/L
You admit patient for midnight cortisol testing…
Explain Type 8 AM plasma cortisol >1.8 µg/dL rules out exogenous hypercortisolism. Overnight dexamethasone suppression test confirms endogenous Cushing syndrome.
What is the next step in management?
You recall Cushing syndrome can be ACTH-dependent or ACTH-independent. You measure plasma ACTH.
Result: ACTH 75 pg/mL (normal < 15 pg/mL)
What is the next best investigation to identify the definitive source of ACTH?
Plasma ACTH: 75 pg/mL (normal < 15 pg/mL) - indicates ACTH-dependent cause.
What is the next best investigation to identify the definitive source of ACTH?
You recall the need to measure ACTH first.
Result: ACTH 75 pg/mL (normal < 15 pg/mL) - indicates ACTH-dependent cause.
What is the next best investigation?
You recall ACTH measurement should come before invasive tests.
Result: ACTH 75 pg/mL (normal < 15 pg/mL) - indicates ACTH-dependent cause.
What is the next best investigation?
ACTH 75 pg/mL rules out adrenal causes. PET scan shows no metastasis - suggesting pituitary origin.
Inferior petrosal sinus sampling: Ratio 3.2
MRI: 4-mm pituitary mass
What is the definitive treatment?
ACTH 75 pg/mL rules out adrenal causes. PET scan shows no metastasis - suggesting pituitary origin.
Inferior petrosal sinus sampling: Ratio 3.2
MRI: 4-mm pituitary mass
What is the definitive treatment?
ACTH 75 pg/mL rules out adrenal causes.
MRI: 4-mm pituitary mass
Inferior petrosal sinus sampling: Ratio 3.2
What is the definitive treatment?
Your effort is appreciated, but ordering adrenal CT despite ACTH 75 pg/mL indicates misunderstanding of Cushing diagnostic pathway. Elevated ACTH clearly points toward ACTH-dependent cause, making adrenal imaging inappropriate. This reflects choosing investigations without clinical algorithm alignment. With more attention to endocrine evaluation sequence, your clinical decisions will improve.
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Excellent! You successfully navigated this complex endocrine presentation, integrating biochemical results, dynamic testing, and imaging findings with exceptional clarity. Your interpretation of midnight cortisol, ACTH levels, dexamethasone testing, and petrosal sinus sampling demonstrates mature understanding of diagnostic endocrinology. Correctly identifying pituitary source and selecting appropriate management represents optimal patient care.
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You ordered the wrong definitive treatment. The patient later presented with severe symptoms and adenoma invasion into adjacent structures. Transsphenoidal surgical resection remains the correct evidence-based definitive treatment.
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Pituitary radiation is not appropriate first-line therapy for ACTH-dependent Cushing syndrome with confirmed pituitary adenoma. Radiation causes collateral damage to normal pituitary tissue, leading to delayed hypopituitarism (adrenal insufficiency, hypothyroidism, hypogonadism). It carries long-term risk of radiation-induced neoplasms (gliomas, meningiomas). Radiation doesn’t provide rapid hypercortisolism control or reduce mass effect in large tumors. Transsphenoidal surgical resection remains the evidence-based definitive treatment.
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