Cushing's Syndrome
Understanding how symptoms present, as well as tolerability for surgery, can help shed light on treatment.
Living with Cushing’s syndrome
Cushing’s syndrome, although rare, significantly impacts the lives of patients who are diagnosed with this condition. These profiles highlight typical patient concerns, and illustrate common symptoms associated with the manifestation of Cushing’s syndrome.
Patient
Franceso
Age: 46 years old
Patient Insight
Francesco has expressed increased difficulty carrying out his routine daily activities, such as exercising at the gym and other fitness activities, because of weakness. The weakness and tiredness are also impacting his relationships with family and friends. He notes feelings of isolation.
Medical Treatment Naïve
No history of medical treatment for hypercortisolism.
Disease
Ectopic ACTH syndrome caused by ACTH-secreting NSCLC (mild, recurrent).
Diagnosed
6 years ago; no suppression of serum cortisol or UFC during high-dose dexamethasone suppression test, BIPSS negative; ACTH-secreting tumor identified by MRI.
Surgery
Surgical resection to remove tumor initially successful.
Signs and Symptoms
- Cortisol levels were normal for 5 years during routine follow-up.
- Over the last year, developed hypertension (142/90 mmHg) and hypokalaemia, and now cortisol levels are uncontrolled again; no tumor visible, BIPSS negative, confirming non-pituitary source of ACTH.
- Experiencing muscle weakness in upper limbs, pain in left hip, fatigue, depression and weight loss.
Relevant Laboratory Parameters
- Current cortisol status: Uncontrolled
- 24-h UFC: 1.9 × ULN and 2.4 × ULN
- LNSC: 3 × ULN
- ACTH: 4 × ULN
- Potassium: 3.2 nmol/L (normal: 3.6–5.2 nmol/L)
Consider management options to control cortisol levels and alleviate comorbidities.
Case details adapted from: Dormoy et al. 2023; Heleno CT et al. 2023; Pivonello et al. 2016; Tanaka et al. 2020; Valassi et al. 2022.
Patient
Ada
Age: 50 years old
Patient Insight
Ada complains of sleep disturbance. Her depression and cognitive impairment, including memory issues and decreased processing speed, are worsening. She feels exhausted all the time.
Medical Treatment Naïve
No history of medical treatment for hypercortisolism.
Disease
ACTH-independent Cushing’s syndrome (moderate, recurrent).
Diagnosed
3 years ago; 1.6 cm right adrenal lesion identified by MRI.
Surgery
Surgical resection to remove adrenal tumor initially successful; no evidence of a tumor remnant visible on MRI; BIPSS negative.
Signs and Symptoms
- Cortisol levels were controlled without the need for intervention for 2 years.
- Recently, began to show symptomatic signs of relapse, including worsening hypertension requiring initiation of antihypertensive medication (155/90 mmHg).
- Episodes of shortness of breath during routine activities over the last 4 months.
- Physical manifestations are worsening, including 10 kg weight gain over 6 months, increased central obesity, appearance of striae and increased dorsocervical fat deposition.
Relevant Laboratory Parameters
- Current cortisol status: Uncontrolled
- 24-h UFC: 2.3 × ULN and 2.8 × ULN
- LNSC: 5 × ULN
- ACTH: 0.3 × ULN (1.2 × LLN)
Consider management options to allow control of hypercortisolism and ensure optimization of antihypertensive medication.
Case details adapted from: Clayton et al. 2022; Malik & Ben-Shlomo 2022; Moyers & Tiemensma 2020; Pivonello et al. 2016; Santos et al. 2019; Tanaka et al. 2020; Santos et al. 2019; Valassi et al. 2022; Varlamov et al. 2021.
Patient
Teresa
Age: 55 years old
Patient Insight
Teresa has expressed embarrassment about her appearance due to weight gain, excessive bruising, hair growth on her face, and sweating. She consistently feels agitated and reports that she is unable to relax.
Medical Treatment Naïve
No surgery; no history of medical treatment for hypercortisolism.
Disease
Cushing’s disease (severe, treatment naïve).
Diagnosed
Within the last year; 11 mm pituitary adenoma confirmed with MRI.
Surgery
Not eligible for surgery (physician judgement); tumor extends into the cavernous sinus.
Signs and Symptoms
- Weight gain (17 lbs. over 6 months without changing diet or lifestyle); dorsocervical and supraclavicular fat deposits; central obesity.
- Osteoporosis.
- Edema in lower legs and ankles; thinning skin; bruises easily.
- Hirsutism
Relevant Laboratory Parameters
- Current cortisol status: Uncontrolled
- 24-h UFC: 5.8 × ULN and 6.1 × ULN
- LNSC: 2 × ULN
- ACTH: 2 × ULN
Consider management options to control cortisol levels and improve clinical manifestations of hypercortisolism.
Case details adapted from: Frara et al. 2022; Gadelha et al. 2022; Pivonello et al. 2016; Pivonello et al. 2020; Valassi et al. 2022.
Patient
Mario
Age: 55 years old
Patient Insight
Mario has commented that because of his muscle weakness and tiredness, he is unable to go about his daily life, including playing with his young grandchildren.
Treatment
Despite attempts to optimize medical therapy since his surgery 5 years ago, Mario’s cortisol levels have not been controlled, nor have they stabilized.
Disease
Cushing’s disease (mild, persistent following surgery).
Diagnosed
Diagnosed 5 years ago; BIPSS confirmed pituitary source of ACTH secretion; 8 mm pituitary adenoma confirmed with MRI.
Surgery
Transsphenoidal surgery to remove pituitary tumor, but cortisol remained uncontrolled.
Signs and Symptoms
Without a consistent reduction in cortisol, Mario has not experienced improvements in his symptoms and comorbidities:
- Hypertension (160/90 mmHg)
- Diabetes
- Increased central obesity with weight gain (24 lbs. since diagnosis)
- Increased appearance of striae
- Osteoporosis
- Muscle weakness in lower limbs
Relevant Laboratory Parameters
- Current cortisol status: Uncontrolled
- 24 h UFC: 1.6 × ULN and 1.3 × ULN
- LNSC: 4 × ULN
- ACTH: 3 × ULN
- HbA1c: 6.9%
Per treatment guidelines, consider repeat surgery, radiation, or adding/adjusting meds. Bilateral adrenalectomy is a last resort if cortisol remains uncontrolled.
Case details adapted from: Antonini et al. 2022; Castinetti et al. 2021; Clayton et al. 2022; Fookeerah & McLean 2021; Frara et al. 2022; Gadelha et al. 2022; Moyers & Tiemensma 2020; Pivonello et al. 2016; Kamińska M et al. 2023; Pivonello et al. 2020; Santos et al. 2019; Valassi et al. 2022; Varlamov et al. 2021.
Patient
Andrea
Age: 47 years old
Patient Insight
Medical therapy for hypercortisolism was initiated 1 week after surgery. After 6 months on treatment, cortisol levels have reduced but remain persistently uncontrolled. Andrea is also experiencing gastrointestinal side effects that impact his adherence to the prescribed medication.
Medical Treatment Naïve
Andrea has not had surgery; no history of medical treatment for hypercortisolism.
Disease
Cushing’s disease (moderate, persistent following surgery).
Diagnosed
Recently diagnosed; BIPSS confirmed pituitary source of ACTH secretion; 4 mm pituitary adenoma identified by MRI.
Surgery
Transsphenoidal surgery to remove pituitary tumor; however, cortisol levels remained high and medical therapy was initiated.
Signs and Symptoms
Signs and symptoms of hypercortisolism were noted by Andrea for at least 3 years prior to diagnosis:
- Increased central obesity and weight gain
- Rounded face
- Muscle weakness in upper limbs
- Increased appearance of striae
- Hypertension (137/89 mmHg)
- Hypokalaemia
- Diabetes
Relevant Laboratory Parameters
- Current cortisol status: Uncontrolled
- 24 h UFC: 3.0 × ULN and 3.3 × ULN
- LNSC: 2 × ULN
- ACTH: 2 × ULN
- Potassium: 3.0 nmol/L (normal: 3.6–5.2 nmol/L)
- HbA1c: 7.1%
Per treatment guidelines, consider adjusting medical therapy to improve adherence, or repeat surgery. If cortisol control remains insufficient, explore radiation therapy options. Bilateral adrenalectomy is a last resort if cortisol remains uncontrolled.
Case details adapted from: Antonini et al. 2022; Castinetti et al. 2021; Clayton et al. 2022; Fookeerah & McLean 2021; Gadelha et al. 2022; Moyers & Tiemensma 2020; Pivonello et al. 2016; Pivonello et al. 2020; Santos et al. 2019; Valassi et al. 2022; Varlamov et al. 2021.
ACTH, adrenocorticotropic hormone; BIPSS, bilateral inferior petrosal sinus sampling; HbA1c, glycated haemoglobin; LNSC, late-night salivary cortisol; MRI, magnetic resonance imaging; UFC, urinary free cortisol; ULN upper limit of normal.
Adult patients with CS who cannot undergo pituitary surgery or for whom surgery has been ineffective
Select a Patient Profile
Patient: Franceso
Age: 46 years old
Patient: Ada
Age: 50 years old
Patient: Teresa
Age: 55 years old
Patient: Mario
Age: 55 years old
Patient: Andrea
Age: 47 years old
The information provided is intended for educational purposes. The fictitious case studies do not refer to any portrayed patients but depict the general aspects and manifestations of Cushing’s syndrome and Cushing’s disease. All photographs are used with permission. No personal medical information is disclosed.
Photos by S. Schirato, sponsored by Recordati AG
The information provided is intended for educational purposes. The fictitious case studies do not refer to any portrayed patients but depict the general aspects and manifestations of Cushing’s syndrome and Cushing’s disease. All photographs are used with permission. No personal medical information is disclosed.
Photos by S. Schirato, sponsored by Recordati AG
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