SUBCLINICAL HYPERCORTISOLISM IN CENTRAL SEROUS CHORIORETINOPATHY Suri N. Appa, MD
Purpose: To describe a case of a patient with chronic central serous chorioretinopathy who was found to have an adrenocorticotropin-secreting pituitary microadenoma despite the absence of many clinical signs of Cushing syndrome. Methods: A retrospective chart review was performed. This study included a 42-year-old white woman with a history of chronic central serous chorioretinopathy. Results: The patient was found to have severe osteoporosis; although many of the classic signs of Cushing syndrome were absent, laboratory studies and neuroimaging suggested the presence of a pituitary microadenoma. Ophthalmic evaluation revealed the presence of bilateral submacular fluid because of chronic multifocal central serous chorioretinopathy. The patient underwent bilateral photodynamic therapy and surgical excision of the pituitary lesion. Pathologic evaluation confirmed that the pituitary lesion was a pituitary microadenoma. Conclusion: Careful attention to the signs of hypercortisolism in patients with central serous chorioretinopathy may aid in detecting underlying systemic pathology. Endocrinology evaluations in patients presenting with any manifestations of Cushing syndrome may be warranted, even if many classic physical findings are absent. RETINAL CASES & BRIEF REPORTS 8:310–313, 2014
Strong evidence exists implicating glucocorticoids as a risk factor for exacerbation of CSC, although the pathophysiologic mechanism is unknown.1,2 Exposure to elevated levels of glucocorticoids either by exogenous or endogenous mechanisms can result in Cushing syndrome. Cushing syndrome is characterized by moon facies, buffalo hump, truncal obesity, muscle weakness, fatigue, purple skin striae, amenorrhea, easy bruising, emotional disturbances, osteoporosis, and hypertension. This report describes a case of a patient with chronic bilateral CSC who was diagnosed with a pituitary microadenoma in the absence of many common physical manifestations of Cushing syndrome.
From the Department of Ophthalmology, Kaiser Permanente, Yorba Linda, California.
C
entral serous chorioretinopathy (CSC) is a condition characterized by leakage of fluid from the choriocapillaris across the retinal pigment epithelium and accumulation under the neurosensory retina in the macula. The affected patients are predominantly men between 30 years and 50 years of age. Central serous chorioretinopathy may present with unifocal or multifocal leakage. In the majority of cases, spontaneous resolution of the subretinal fluid and recovery of vision can be expected. In some cases, however, the subretinal fluid can persist chronically and can lead to significant permanent loss of vision.
Case Report A 42-year-old white woman with a history of chronic CSC of 4-year duration was referred to our department for treatment of chronic CSC. Ocular examination, macular optical coherence tomography examination, and fluorescein angiography confirmed the presence of subretinal fluid and chronic pigment epithelial changes consistent with chronic bilateral CSC (Figures 1 and 2). She underwent bilateral low-fluence
None of the authors have any financial/conflicting interests to disclose. Presented at the Pacific Retina Study Club Meeting, Los Angeles, CA, April 19, 2013. Reprint requests: Suri N. Appa, MD, Department of Ophthalmology, Kaiser Permanente, 2521 Michelle, Tustin, CA 92780; e-mail: [email protected]
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Fig. 1. Before photodynamic therapy, subretinal fluid was seen on a macula OCT scan of the right eye (A) and left eye (B).
photodynamic therapy with multiple spots in each eye. Macular optical coherence tomography examination 4 weeks after treatment showed resolution of the subretinal fluid in both eyes (Figure 3). Five months before presenting to our clinic, the patient suddenly awoke one morning with left-sided chest wall pain. Two days after the onset of pain, she visited her primary care physician. Her medical history included hypertension of 10-year duration controlled on 3 medications, migraine headaches, chronic back pain, and multiple metatarsal stress fractures. Rib x-rays revealed multiple left-sided rib fractures. A bone density test was ordered, which showed a lowest Z-score of −2.2 suggesting significant osteoporosis compared with an age-
311
Fig. 2. Fluorescein angiography showed multifocal hyperfluorescent spots and multiple areas of mottled hyperfluorescent RPE changes, including evidence of gravitational staining patterns in the right eye (A) and left eye (B), consistent with chronic multifocal central serous retinopathy.
matched control population. An endocrinology consultation was obtained. On review of systems, the patient complained of increased migraine symptoms, fatigue, and body ache over the previous 6 months. She denied any menstrual irregularities or weight gain. Physical examination revealed mild hirsutism on the chin and mild bruising of the skin. The findings of moon facies, buffalo hump, supraclavicular fat pad, truncal obesity, purple striae, acne, and acanthosis nigricans were absent. Laboratory evaluation revealed mild elevation of cortisol in a 24-hour urine collection. A low-dose dexamethasone suppression
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Fig. 4. T1-weighted gadolinium-enhanced MRI scan of the brain showed a hypointense area of the right anterior pituitary gland.
transsphenoidal endoscopic excision of the pituitary lesion. Surgical pathology evaluation confirmed that the lesion was a pituitary microadenoma.
Discussion
Fig. 3. After photodynamic therapy, a macula OCT scan of the right eye (A) and left eye (B) showed resolution of the subretinal fluid.
test failed to suppress the serum cortisol level. A high-dose dexamethasone suppression test did suppress the serum cortisol level. Based on the laboratory data, an adrenocorticotropinproducing pituitary adenoma was suspected. An MRI of the sella turcica revealed a 4 · 3 mm hypointense lesion on the right side of the anterior pituitary gland (Figure 4). The patient was referred to an interventional radiologist for further evaluation of the pituitary lesion seen on MRI. Inferior petrosal sinus sampling was performed, which confirmed a significantly higher ratio of serum adrenocorticotropin hormone concentration in the right inferior petrosal sinus compared with the peripheral vein, consistent with an adrenocorticotropinsecreting pituitary adenoma. The patient elected to undergo
Endogenous Cushing syndrome can occur from excessive pituitary or ectopic production of adrenocorticotropin hormone (ACTH) or from autonomous secretion of cortisol from adrenal pathology. European epidemiologic studies have estimated the incidence to be approximately 2 to 3 cases per million, and women are affected more frequently than men.3 Several authors have reported the coexistence of endogenous Cushing syndrome and CSC. Bouzas et al4 reported that in a consecutive series of 60 patients with endogenous Cushing syndrome, 3 had CSC. Wang and Saha5 reported that a patient with a pituitary microadenoma developed bilateral multifocal CSC, which subsequently improved after resection of the tumor. Iannetti et al6 and Cunneen et al,7 each reported diagnosing endogenous Cushing syndrome in a patient who initially presented with CSC. This patient with bilateral chronic CSC was found to have an adrenocorticotropin-producing pituitary adenoma. She exhibited mild facial hirsutism, mild skin bruising, osteoporosis, and hypertension, but the other classic Cushingoid findings were absent. Subclinical hypercortisolism is a term used to describe the condition of excess serum cortisol without the identification of overt specific signs of Cushing syndrome. It is believed although that many patients considered to have subclinical hypercortisolism, actually do manifest some Cushingoid features on careful
313
SUBCLINICAL HYPERCORTISOLISM IN CSC
examination.8 The patient described suffered from hypertension and osteoporosis, which can be considered part of but not specific for Cushing syndrome. Other characteristic features of the syndrome were either subtle or absent. This case raises the awareness that some patients may be significantly affected by hypercortisolism without exhibiting an obvious Cushingoid appearance. Recognizing hypercortisolism in patients with CSC is important not only to identify a potential cause of vision loss, but also prevent premature osteoporosis as well as cardiovascular morbidity and mortality. Careful attention to the signs of hypercortisolism in patients with CSC may be a clue to underlying systemic pathology. Endocrinology evaluations in patients presenting with any manifestations of Cushing syndrome may be warranted even if many classic physical findings are absent. Key words: central serous chorioretinopathy, cortisol, Cushing syndrome, glucocorticoid, pituitary microadenoma, subclinical hypercortisolism.
References 1. Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol 2002;47:431–448. 2. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109:1834–1837. 3. Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1526–1540. 4. Bouzas EA, Scott MH, Mastorakos G, et al. Central serous chorioretinopathy in endogenous hypercortisolism. Arch Ophthalmol 1993;111:1229–1233. 5. Wang BZ, Saha N. Bilateral multifocal central serous chorioretinopathy in endogenous hypercortisolism. Clin Exp Optom 2011;94:598–599. 6. Iannetti L, Spinucci G, Pesci FR, et al. Central serous chorioretinopathy as a presenting symptom of endogenous Cushing syndrome: a case report. Eur J Ophthalmol 2011;21:661–664. doi:10.5301/EJO.2011.6449. 7. Cunneen TS, Tridgell D. The dexamethasone suppression test for the diagnosis of Cushing syndrome in a patient with central serous chorioretinopathy. Retin Cases Brief Rep 2013;7:143–145. 8. Chiodini I. Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab 2011;96:1223–1236.
Purpose: To describe a case of a patient with chronic central serous chorioretinopathy who was found to have an adrenocorticotropin-secreting pituitary microadenoma despite the absence of many clinical signs of Cushing syndrome. Methods: A retrospective chart review was performed. This study included a 42-year-old white woman with a history of chronic central serous chorioretinopathy. Results: The patient was found to have severe osteoporosis; although many of the classic signs of Cushing syndrome were absent, laboratory studies and neuroimaging suggested the presence of a pituitary microadenoma. Ophthalmic evaluation revealed the presence of bilateral submacular fluid because of chronic multifocal central serous chorioretinopathy. The patient underwent bilateral photodynamic therapy and surgical excision of the pituitary lesion. Pathologic evaluation confirmed that the pituitary lesion was a pituitary microadenoma. Conclusion: Careful attention to the signs of hypercortisolism in patients with central serous chorioretinopathy may aid in detecting underlying systemic pathology. Endocrinology evaluations in patients presenting with any manifestations of Cushing syndrome may be warranted, even if many classic physical findings are absent. RETINAL CASES & BRIEF REPORTS 8:310–313, 2014
Strong evidence exists implicating glucocorticoids as a risk factor for exacerbation of CSC, although the pathophysiologic mechanism is unknown.1,2 Exposure to elevated levels of glucocorticoids either by exogenous or endogenous mechanisms can result in Cushing syndrome. Cushing syndrome is characterized by moon facies, buffalo hump, truncal obesity, muscle weakness, fatigue, purple skin striae, amenorrhea, easy bruising, emotional disturbances, osteoporosis, and hypertension. This report describes a case of a patient with chronic bilateral CSC who was diagnosed with a pituitary microadenoma in the absence of many common physical manifestations of Cushing syndrome.
From the Department of Ophthalmology, Kaiser Permanente, Yorba Linda, California.
C
entral serous chorioretinopathy (CSC) is a condition characterized by leakage of fluid from the choriocapillaris across the retinal pigment epithelium and accumulation under the neurosensory retina in the macula. The affected patients are predominantly men between 30 years and 50 years of age. Central serous chorioretinopathy may present with unifocal or multifocal leakage. In the majority of cases, spontaneous resolution of the subretinal fluid and recovery of vision can be expected. In some cases, however, the subretinal fluid can persist chronically and can lead to significant permanent loss of vision.
Case Report A 42-year-old white woman with a history of chronic CSC of 4-year duration was referred to our department for treatment of chronic CSC. Ocular examination, macular optical coherence tomography examination, and fluorescein angiography confirmed the presence of subretinal fluid and chronic pigment epithelial changes consistent with chronic bilateral CSC (Figures 1 and 2). She underwent bilateral low-fluence
None of the authors have any financial/conflicting interests to disclose. Presented at the Pacific Retina Study Club Meeting, Los Angeles, CA, April 19, 2013. Reprint requests: Suri N. Appa, MD, Department of Ophthalmology, Kaiser Permanente, 2521 Michelle, Tustin, CA 92780; e-mail: [email protected]
310
SUBCLINICAL HYPERCORTISOLISM IN CSC
Fig. 1. Before photodynamic therapy, subretinal fluid was seen on a macula OCT scan of the right eye (A) and left eye (B).
photodynamic therapy with multiple spots in each eye. Macular optical coherence tomography examination 4 weeks after treatment showed resolution of the subretinal fluid in both eyes (Figure 3). Five months before presenting to our clinic, the patient suddenly awoke one morning with left-sided chest wall pain. Two days after the onset of pain, she visited her primary care physician. Her medical history included hypertension of 10-year duration controlled on 3 medications, migraine headaches, chronic back pain, and multiple metatarsal stress fractures. Rib x-rays revealed multiple left-sided rib fractures. A bone density test was ordered, which showed a lowest Z-score of −2.2 suggesting significant osteoporosis compared with an age-
311
Fig. 2. Fluorescein angiography showed multifocal hyperfluorescent spots and multiple areas of mottled hyperfluorescent RPE changes, including evidence of gravitational staining patterns in the right eye (A) and left eye (B), consistent with chronic multifocal central serous retinopathy.
matched control population. An endocrinology consultation was obtained. On review of systems, the patient complained of increased migraine symptoms, fatigue, and body ache over the previous 6 months. She denied any menstrual irregularities or weight gain. Physical examination revealed mild hirsutism on the chin and mild bruising of the skin. The findings of moon facies, buffalo hump, supraclavicular fat pad, truncal obesity, purple striae, acne, and acanthosis nigricans were absent. Laboratory evaluation revealed mild elevation of cortisol in a 24-hour urine collection. A low-dose dexamethasone suppression
312
RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 4
Fig. 4. T1-weighted gadolinium-enhanced MRI scan of the brain showed a hypointense area of the right anterior pituitary gland.
transsphenoidal endoscopic excision of the pituitary lesion. Surgical pathology evaluation confirmed that the lesion was a pituitary microadenoma.
Discussion
Fig. 3. After photodynamic therapy, a macula OCT scan of the right eye (A) and left eye (B) showed resolution of the subretinal fluid.
test failed to suppress the serum cortisol level. A high-dose dexamethasone suppression test did suppress the serum cortisol level. Based on the laboratory data, an adrenocorticotropinproducing pituitary adenoma was suspected. An MRI of the sella turcica revealed a 4 · 3 mm hypointense lesion on the right side of the anterior pituitary gland (Figure 4). The patient was referred to an interventional radiologist for further evaluation of the pituitary lesion seen on MRI. Inferior petrosal sinus sampling was performed, which confirmed a significantly higher ratio of serum adrenocorticotropin hormone concentration in the right inferior petrosal sinus compared with the peripheral vein, consistent with an adrenocorticotropinsecreting pituitary adenoma. The patient elected to undergo
Endogenous Cushing syndrome can occur from excessive pituitary or ectopic production of adrenocorticotropin hormone (ACTH) or from autonomous secretion of cortisol from adrenal pathology. European epidemiologic studies have estimated the incidence to be approximately 2 to 3 cases per million, and women are affected more frequently than men.3 Several authors have reported the coexistence of endogenous Cushing syndrome and CSC. Bouzas et al4 reported that in a consecutive series of 60 patients with endogenous Cushing syndrome, 3 had CSC. Wang and Saha5 reported that a patient with a pituitary microadenoma developed bilateral multifocal CSC, which subsequently improved after resection of the tumor. Iannetti et al6 and Cunneen et al,7 each reported diagnosing endogenous Cushing syndrome in a patient who initially presented with CSC. This patient with bilateral chronic CSC was found to have an adrenocorticotropin-producing pituitary adenoma. She exhibited mild facial hirsutism, mild skin bruising, osteoporosis, and hypertension, but the other classic Cushingoid findings were absent. Subclinical hypercortisolism is a term used to describe the condition of excess serum cortisol without the identification of overt specific signs of Cushing syndrome. It is believed although that many patients considered to have subclinical hypercortisolism, actually do manifest some Cushingoid features on careful
313
SUBCLINICAL HYPERCORTISOLISM IN CSC
examination.8 The patient described suffered from hypertension and osteoporosis, which can be considered part of but not specific for Cushing syndrome. Other characteristic features of the syndrome were either subtle or absent. This case raises the awareness that some patients may be significantly affected by hypercortisolism without exhibiting an obvious Cushingoid appearance. Recognizing hypercortisolism in patients with CSC is important not only to identify a potential cause of vision loss, but also prevent premature osteoporosis as well as cardiovascular morbidity and mortality. Careful attention to the signs of hypercortisolism in patients with CSC may be a clue to underlying systemic pathology. Endocrinology evaluations in patients presenting with any manifestations of Cushing syndrome may be warranted even if many classic physical findings are absent. Key words: central serous chorioretinopathy, cortisol, Cushing syndrome, glucocorticoid, pituitary microadenoma, subclinical hypercortisolism.
References 1. Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol 2002;47:431–448. 2. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109:1834–1837. 3. Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1526–1540. 4. Bouzas EA, Scott MH, Mastorakos G, et al. Central serous chorioretinopathy in endogenous hypercortisolism. Arch Ophthalmol 1993;111:1229–1233. 5. Wang BZ, Saha N. Bilateral multifocal central serous chorioretinopathy in endogenous hypercortisolism. Clin Exp Optom 2011;94:598–599. 6. Iannetti L, Spinucci G, Pesci FR, et al. Central serous chorioretinopathy as a presenting symptom of endogenous Cushing syndrome: a case report. Eur J Ophthalmol 2011;21:661–664. doi:10.5301/EJO.2011.6449. 7. Cunneen TS, Tridgell D. The dexamethasone suppression test for the diagnosis of Cushing syndrome in a patient with central serous chorioretinopathy. Retin Cases Brief Rep 2013;7:143–145. 8. Chiodini I. Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab 2011;96:1223–1236.
